Abstract
The functions assumed by free cholesterol in mammalian cells are diverse, ranging from that as a starting substrate for the synthesis of steroid hormones and bile salts to its less specifically understood but critical role as a principal lipid component of every cell membrane. Cholesterol biosynthesis begins with metabolically supplied cytoplasmic acetyl CoA that also serves as the common precursor for de novo fatty acid synthesis, and can be expressed by the reaction: 18 acetyl CoA + 1/2O2 + 10 H+ → cholesterol + 9 CO2 +18 CoA-SH. During the synthesis, the genesis of mevalonic acid (MVA) from 3-hydroxy-3-methylglutaryl CoA (HMG-CoA), catalyzed by HMG-CoA reductase (HMGR), the third and principal rate-controlling enzyme of the pathway, leads to the production of diverse polyisoprenoid intermediates. Metabolism of MVA demonstrates considerable versatility through ensuing branching reactions that yield a host of terpene compounds used in the construction of an assortment of required metabolites [dolichol, ubiquinone(Coenzyme Q), isopentenyl adenine, heme a/a3], in addition to cholesterol itself. This chapter focuses on associations that link cholesterol and mitochondrial citrate export, as well as the metabolism of citrate-derived isoprenoid metabolites en route to cholesterol synthesis, with deregulated cell proliferation (i.e., cancer).
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References
Adamson, P., Marshall, C. J., Hall, A., and Tilbrook, P. A., 1992, Post-translational modifications of p21 rho proteins, J. Biol. Chem. 267:20033–20038.
Agarwal, S., Corbley, M. J., and Roberts, T. M., 1995, Reconstitution of signal transduction from the membrane to the nucleus in a baculovirus expression system: activation of Raf-1 leads to hyper-modificatio of c-jun and c-fos via multiple pathways, Oncogene 11:427–438.
Akopyan, T. N., Couedel, Y., Orlowski, M., Fournie-Zaluski, M. C., and Roques, B. P., 1994, Proteolytic processing of famesylated peptides: assay and partial purification from pig brain membranes of an endopeptidase which has the characteristics of E.C. 3.4.24.15, Biochem. Biophys. Res. Com-mun. 198:787–794.
Alberts, A., Chen, J., Kuron, G., Hunt, V., Huff, J., Hoffman, C., Rothrock, J., Lopez, M., Joshua, H., Harris, E., Patchett, A., Monaghan, R., Currie, S., Stapley, E., Albers-Schonberg, G., Hensens, O., Hirshfield, J., Hoogsteen, K., Liesch, J., and Springer, J., 1980, Mevinolin: a highly potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase and a cholesterol-lowering agent, Proc. Natl. Acad. Sci. USA 77:3957–3961.
Appelkvist, E. L., Reinhart, M., Fischer, R., Billheimer, J., and Daliner, G., 1990, Presence of individual enzymes of cholesterol biosynthesis in rat liver peroxisomes, Arch. Biochem. Biophys. 282: 318–325.
Appelkvist, E. L., Grünler, J., and Dallner, G., 1995, Isoprenoid biosynthesis in peroxisomes, FASEB J. 9:A1312.
Armstrong, S. A., Hannah, V. C., Goldstein, J. L., and Brown, M. S., 1995, CAAX geranylger-anyl transferase transfers farnesyl as efficiently as geranylgeranyl to RhoB, J. Biol. Chem. 270:7864–7868.
Aronheim, A., Engelberg, D., Li, N., Al-Alawi, N., Schlessinger, J., and Karin, M., 1994, Membrane targeting of the nucleotide exchange factor Sos is sufficient for activating the Ras signaling pathway, Cell 78:949–961.
Azarnoff, D. L., Tucker, D. R., and Barr, G. A., 1965, Studies with ethyl chlorophenoxyisobutyrate (Clofibrate), Metabolism 14:959–965.
Azrolan, N. I., and Coleman, P. S., 1989, A discoordinate increase in the cellular amount of 3-hydroxy-3-methylglutaryl-CoA reductase results in the loss of rate-limiting control over cholesterogenesis in a tumor cell-free system, Biochem. J. 258:421–425.
Barbacid, M., 1987, ras genes, Annu. Rev. Biochem. 56:779–827.
Biardi, L., Sreedhar, A., Zokaei, A., Vartak, N. B., Bozeat, R. L., Shackelford, J. E., Keller, G. A., and Krisans, S. K., 1994, Mevalonate kinase is predominantly localized in peroxisomes and is defective in patients with peroxisome deficiency disorders, J. Biol. Chem. 269:1197–1205.
Bilger, B., 1995, Forever young, The Sciences 35:26–30.
Bishop, J. M., 1991, Molecular themes in oncogenesis, Cell 64:235–248.
Black, S. D., 1992, Development of hydrophobicity parameters for prenylated proteins, Biochem. Biophys. Res. Commun. 186:1437–1442.
Blenis, J., 1993, Signal transduction via MAP kinases: proceed at your own RSK, Proc. Natl. Acad. Sci. USA 90:5889–5892.
Blouin, A., Bolender, R. P., and Weibel, E. R., 1977, Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma, J. Cell Biol. 72: 441–455.
Boctor, A. M., and Bystryn, J.-C, 1982, Degradation of tumor-associated antigens shed by human melanoma cells in culture, Cancer Res. 42:2121–2125.
Boguski, M. S., and McCormick, F., 1993, Proteins regulating Ras and its relatives, Nature 366: 643–654.
Bradfute, D. L., and Simoni, R. D., 1994, Non-sterol compounds that regulate cholesterogenesis: analogues of farnesyl pyrophosphate reduce 3-hydroxy-3-methylglutaryl-coenzyme A reductase levels, J. Biol. Chem. 269:6645–6650.
Braun, P.E., De Angelis, D., Shtybel, W. W., and Bernier, L., 1991, Isoprenoid modification permits 2’,3’-cyclic nucleotide 3′-phosphodiesterase to bind to membranes, J. Neurosci. Res. 30:540–544.
Brenneman, D. E., Mathur, S. N., and Spector, A. A., 1975, Characterization of the hyperlipidemia in mice bearing the Ehrlich ascites tumor, Eur. J. Cancer 11:225–230.
Brown, M. S., and Goldstein, J. L., 1980, Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth, J. Lipid Res. 21:505–517.
Brown, M. S., Faust, J. R., Goldstein, J. L., Kaneko, I., and Endo, A., 1978, Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts incubated with compactin (ML-236B), a competitive inhibitor of the reductase, J. Biol. Chem. 253:1121–1128.
Brown, M. S., Goldstein, J. L., Paris, K. J., Burnier, J. P., and Masters, J. C., Jr., 1992, Tetrapeptide inhibitors of protein:farnesyltransferase: amino-terminal substitution in phenylalanine-containing tetrapeptides restores farnesylation, Proc. Natl. Acad. Sci. USA 89:8313–8316.
Bruenger, E., and Rilling, H. C., 1986, Prenylated proteins from kidney, Biochem. Biophys. Res. Commun. 139:209–214.
Bruscalupi, G., Castellano, F., Sacco, S., and Trentalance, A., 1994, Prenylated proteins in regenerating rat liver, Biochem. Biophys. Res. Commun. 200:1713–1720.
Bryla, J., 1981, Inhibitors of mitochondrial anion transport, Inhibitors of Mitochondrial Function (M. Erecinska and D. F. Wilson, eds.), pp. 211–259, Pergamon Press, New York.
Buchwald, H., 1992, Cholesterol inhibition, cancer, and chemotherapy, Lancet 339:1154–1156.
Bukhtiyarov, Y. E., Omer, C. A., and Allen, C. M., 1995, Photoreactive analogues of prenyl diphosphates as inhibitors and probes of human protein farnesyltransferase and geranylgeranyltrans-ferase type I, J. Biol. Chem. 270:19035–19040.
Call, T. G., Stenson, M. J., and Witzig, T. E., 1994, Effects of phenylacetate on cells from patients with B-chronic lymphocytic leukemia, Leukemia Lymphoma 14:145–149.
Carboni, J. M., Yan, N., Cox, A. D., Bustelo, X., Graham, S. M., Lynch, M. J., Weinmann, R., Seizinger, B. R., Der, C. J., Barbacid, M., and Manne, V., 1995, Farnesyltransferase inhibitors are inhibitors of Ras but not R-Ras2/TC21 transformation, Oncogene 10:1905–1913.
Casey, P. J., 1995, Protein lipidation in cell signaling, Science 268:221–225.
Casey, P. J., and Seabra, M. C., 1996, Protein Prenyltransferases, J. Biol. Chem. 271: 5289–5292.
Castillo, M., Burgos, C., Rodriques-Vico, R., Zafra, M. F., and Garcia-Peregrin, E., 1990, Effects of Clofibrate on the main regulatory enzymes of cholesterogenesis, Life Sci. 46:397–403.
Castillo, M., Iglesias, J., Zafra, M. F., and Garcia-Peregrin, E., 1991a, Inhibition of chick brain cho-lesterogenic enzymes by phenyl and phenolic derivatives of phenylalanine, Neurochem. Int. 18: 171–174.
Castillo, M., Martinez-Cayuela, M., Zafra, M. F., and Garcia-Peregrin, E., 1991b, Effect of phenylalanine derivatives on the main regulatory enzymes of hepatic cholesterogenesis, Mol. Cell. Biochem. 105:21–25.
Chan, A. M.-L., Miki, T., Meyers, K., and Aaronson, S. A., 1994, A human oncogene of the RAS superfamily unmasked by expression cDNA cloning, Proc. Natl. Acad. Sci. USA 91:7558–7562.
Chazotte, B., and Hackenbrock, C. R., 1988, The multicollisional, obstructed, long-range diffusional nature of mitochondrial electron transport, J. Biol. Chem. 263:14359–14367.
Chazotte, B., and Hackenbrock, C.R., 1991, Modulation and analysis of structure and function of the inner mitochondrial membrane through the application of phospholipid enrichment and membrane fusion techniques, Membrane Fusion (J. Wilschut and D. Hoekstra, eds.), pp. 803–844, Marcel Dekker, New York.
Chen, H., Born, E., Mathur, S. N., and Field, F. J., 1993, Cholesterol and sphingomyelin syntheses are regulated independently in cultured intestinal cells, CaCo-2: role of membrane cholesterol and sphingomyelin content, J. Lipid Res. 34:2159–2167.
Chen, H. W., 1984, Role of cholesterol metabolism in cell growth, Fed. Proc. 43:126–130.
Chen, H. W., Heiniger, H.-J. and Kandutsch, A. A., 1975, Relationship between sterol synthesis and DNA synthesis in phytohemagglutinin-stimulated mouse lymphocytes, Proc. Natl. Acad. Sci. USA 72: 1950–1954.
Chen, H. W., Kandutsch, A. A., and Heiniger, H.-J., 1978, The role of cholesterol in malignancy, Prog. Exp. Tumor Res. (D. F. H. Wallach, ed.), pp. 275–316, S. Karger, Basel.
Chen, W.-J., Andres, D., Goldstein, J. L., Russell, D., and Brown, M., 1991, cDNA cloning and expression of the peptide-binding subunit of rat p21ras farnesyltransferase, the counterpart of yeast DPR1/RAM1, Cell 66:327–334.
Chen, W.-J., Moomaw, J. F., Overton, L., Kost, T. A., and Casey, P., 1993, High level expression of mammalian protein farnesyltransferase in a baculovirus system, J. Biol. Chem. 268: 9675–9680.
Chin, C. J., Luskey, K. L., Anderson, R. G. W., Faust, J. R., Goldstein, J. L., and Brown, M. S., 1982, Appearance of crystalloid endoplasmic reticulum in compactin-resistant Chinese hamster cells with a 500-fold increase in 3-hydroxy-3-methylglutaryl-coenzyme A reductase, Proc. Natl. Acad. Sci. USA 79:1185–1189.
Cinatl, J., Cinatl, J., Mainke, M., Weissflog, A., Rabenau, H., Kornhuber, B., and Doerr, H. W., 1993, In vitro differentiation of human neuroblastoma cells by sodium phenylacetate, Cancer Lett. 70:15–24.
Cinatl, J., Cinatl, J., Herneiz, P., Rabenau, H., Novak, M., Benda, R., Giimbel, H., Kornhuber, B., and Doerr, H. W., 1994, Induction of myogenic differentiation in a human rhabdomyosarcoma cell line by phenylacetate, Cancer Lett. 78:41–48.
Clarke, S., 1992, Protein isoprenylation and methylation at carboxy-terminal cysteine residues, Annu. Rev. Biochem. 61:355–386.
Clarke, S., Vogel, J., Deschenes, R., and Stock, J., 1988, Post-translational modification of the H-ras oncogene protein: evidence for a third class of protein carboxyl methyltransferase, Proc. Natl. Acad. Sci. USA 85:4643–4647.
Clegg, R. J., Middleton, B., Bell, G. D., and White, D. A., 1980, Inhibition of hepatic cholesterol synthesis and 3-hyroxy-3-methylglutaryl coenzyme A reductase by mono and bicyclic monoterpenes administered in vivo, Biochem. Pharmacol. 29:2125–2127.
Clegg, R. J., Middleton, B., Bell, G. D., and White, D. A., 1982, The mechanism of cyclic monoter-pene inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase in vivo in the rat, J. Biol. Chem. 257:2294–2299.
Cohen, B. I., Raicht, R. F., Shefer, S., and Mosbach, E. H., 1974, Effects of Clofibrate on sterol metabolism in the rat, Biochim. Biophys. Acta 369:79–85.
Cohen, L. H., Valentijn, A. R. P. M., Roodenburg, L., van Leeuwen, R. E. W., Huisman, R. H., Lutz, R. J., van der Marel, G. A., and van Boom, J. H., 1995, Different analogs of farnesyl pyrophosphate inhibit squalene synthase and protein:farnesyltransferase to different extents, Biochem. Pharmacol. 49:839–845.
Coleman, P. S., 1986a, Membrane cholesterol and tumor bioenergetics, Ann. NY Acad. Sci. 488: 451–467.
Coleman, P. S., 1986b, The mitochondrial citrate transport carrier and the role of deregulated choles-terogenesis in tumor cell proliferation, EBEC Reports 4:11.
Coleman, P. S., 1991, Deterministic coupling between cellular bioenergetics, cholesterol synthesis, cell proliferation and cancer, Chemical Carcinogenesis 2: Modulating Factors (A. Columbano, F. Feo, R. Pascale, and P. Pani, eds.), pp. 265–288, Springer Science+Business Media New York.
Coleman, P. S., and Lavietes, B. B., 1981, Membrane cholesterol, tumorigenesis, and the biochemical phenotype of neoplasia, CRC Crit. Rev. Biochem. 11:341–393.
Coleman, P. S., and Sepp-Lorenzino, L., 1990, The role of the cholesterol synthesis pathway during tumor cell proliferation, Adv. Cholesterol Res. (M. Esfaham and J. Swaney, eds.), pp. 201–270, Telford Press, NJ.
Coleman, P. S., Lavietes, B., Born, R., and Weg, A., 1978, Cholesterol enrichment of normal mitochondria in vitro: a model system with properties of hepatoma mitochondria, Biochem. Biophys. Res. Commun. 84:202–207.
Corsini, A., Verri, D., Raiteri, M., Quarato, M., Paoletti, R., and Fumagalli, R., 1995, Effects of 26-aminocholesterol, 27-hydroxycholesterol and 25-hydroxycholesterol on proliferation and cholesterol homeostasis in arterial monocytes, Arterio. Throm. Vasc. Biol. 15:420–428.
Cox, A. D., and Der, C. J., 1992, The ras/cholesterol connection: implications for ras oncogenicity, Crit. Rev. Oncogen. 3:365–400.
Cox, D. C., Comai, K., and Goldstein, A. L., 1988, Effects of cholesterol and 25-hydroxycholesterol on smooth muscle cell and endothelial cell growth, Lipids 23:85–88.
Cox, A. D., Garcia, A. M., Westwick, J. K., Kowalczyk, J. J., Lewis, M. D., Brenner, D. A., and Der, C. J., 1994, The CAAX peptidomimetic compound B581 specifically blocks farnesylated, but not geranylgeranylated or myristoylated, oncogenic ras signaling and transformation, J. Biol. Chem. 269:19203–19206.
Crowell, P. L., and Gould, M. N., 1994, Chemoprevention and therapy of cancer by d-limonene, Crit. Rev. Oncogenesis 5:1–22.
Crowell, P. L., Chang, R., Ren, Z., Elson, C., and Gould, M., 1991, Selective inhibition of isoprenylation of 21-26-kDa proteins by the anticarcinogen d-limonene and its metabolites, J. Biol. Chem. 266:17679–17685.
Crowell, P. L., Lin, S., Vedejs, E., and Gould, M. N., 1992, Identification of circulating metabolites of the antitumor agent d-limonene capable of inhibiting protein isoprenylation and cell growth, Cancer Chemoth. Pharmacol. 31:205–212.
Crowell, P. L., Ren, Z., Lin, S., Vedejs, E., and Gould, M. N., 1994, Structure-activity relationships among monoterpene inhibitors of protein isoprenylation and cell proliferation, Biochem. Pharmacol 47:1405–1415.
Cuthbert, J. A., and Lipsky, P. E., 1991, Negative regulation of cell proliferation by mevalonate or one of the mevalonate phosphates, J. Biol. Chem. 266:17966–17971.
Cuthbert, J. A., and Lipsky, P. E., 1995, Suppression of the proliferation of ras-transformed cells by fluoromevalonate, an inhibitor of mevalonate metabolism, Cancer Res. 55:1732–1740.
Dalton, M. B., Fantle, K. S., Bechtold, H. A., DeMaio, L., Evans, R. M., Krystosek, A., and Sinensky, M., 1995, The farnesyl protein transferase inhibitor BZA-5B blocks farnesylation of nuclear lamins and p21ras but does not affect their function or localization, Cancer Res. 55: 3295–3304.
Das, N. P., and Allen, C. M., 1991, Inhibition of farnesyl transferases from malignant and non-malignant cultured human lymphocytes by prenyl substrate analogues, Biochem. Biophys. Res. Commun. 181:729–735.
Daum, G., 1985, Lipids of mitochondria, Biochim. Biophys. Acta 822:1–42.
Davis, R. J., 1993, The mitogen-activated protein kinase signal transduction pathway, J. Biol. Chem. 268:14553–14556.
DeClue, J. E., Vass, W. C., Papageorge, A. G., Lowy, D. R., and Willumsen, B. M., 1991, Inhibition of cell growth by lovastatin is independent of ras function, Cancer Res. 51:712–717.
Dessi, S., Batetta, B., Anchisi, C., Pani, P., and Costelli, P., 1992, Cholesterol metabolism during the growth of a rat ascites hepatoma (Yoshida AH-130), Br. J. Cancer 66:787–793.
Dietschy, J. M., and Siperstein, M. D., 1967, Effect of cholesterol feeding and fasting on sterol synthesis in seventeen tissues of the rat, J. Lipid Res. 8:97–104.
Downward, J., 1990, The ras superfamily of small GTP-binding proteins, Trends Biochem. Sci. 15: 469–472.
Doyle, J., Kabakoff, B., and Kandutsch, A. A., 1991, Dolichyl phosphate as a regulator of cell growth, Chemical Carcinogenesis-2: Modulating Factors (A. Columbano, F. Feo, R. Pascale, and P. Pani, eds.), pp. 289–297, Springer Science+Business Media New York.
Echegoyen, S., Oliva, E. B., Sepulveda, J., Diaz-Zagoya, J. C., Espinosa-Garcia, M. T., Pardo, J. P., and Martinez, F., 1993, Cholesterol increase in mitochondria: its effect on inner-membrane functions, submitochondrial localization and ultrastructure morphology, Biochem. J. 289: 703–708.
Edwards, P. A., Lan, S.-F., and Fogelman, A. M., 1984, High density lipoproteins and lecithin dispersions increase the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase by increasing the rate of synthesis and decreasing the rate of degradation of the enzyme, J. Biol. Chem. 259: 8190–8194.
Elson, C. E., and Yu, S. G., 1994, The chemoprevention of cancer by mevalonate-derived constituents of fruits and vegetables, J. Nutrit. 124:607–614.
Endo, A., 1992, The discovery and development of HMG-CoA reductase inhibitors, J. Lipid Res. 33:1569–1582.
Endo, A., Kuroda, M., and Tanazawa, K., 1976, Competitive inhibition of 3-hydroxy-3-methylglutaryl CoA reductase by ML-236A and ML-236B, fungal metabolites having hypocholesterolemic activity, FEBS Lett. 72:323–325.
Ericsson, J., Appelkvist, E. L., Runquist, M., and Dallner, G., 1993, Biosynthesis of dolichol and cholesterol in rat liver peroxisomes, Biochimie 75:167–173.
Fairbanks, K. P., Witte, L. D., and Goodman, D. S., 1984, Relationship between mevalonate and mitogenesis in human fibroblasts stimulated with platelet-derived growth factor, J. Biol. Chem. 259:1546–1551.
Fairbanks, K. P,Barbu, V. D., Witte, L. D., Weinstein, I. B., and Goodman, D. S., 1986, Effects of me vi-nolin and mevalonate on cell growth in several transformed cell lines, J. Cell. Physiol 127:216–222.
Farias, R. N., Bloj, B., Morero, R. D., Sineriz, F., and Trucco, R. E., 1975, Regulation of allosteric membrane-bound enzymes through changes in membrane lipid composition, Biochim. Biophys. Acta 415:231–254.
Farnsworth, C. C., Gelb, M. H., and Glomset, J. A., 1990, Identification of geranylgeranyl-modified proteins in HeLa cells, Science 247:320–322.
Farnsworth, C. C., Yamane, H., Gelb, M., and Glomset, J. A., 1990, A 23 kDa GTP-binding protein from bovine brain membranes is geranylgeranylated, FASEB J. 4:870a.
Faust, J. R., Lusky, K. L., Chin, D. J., Goldstein, J. L., and Brown, M. S., 1982, Regulation of synthesis and degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase by low density lipoprotein and 25-hydroxycholesterol in UT-1 cells, Proc. Natl Acad. Sci. USA 79:5205–5209.
Feo, F., Canuto, R. A., Bertone, G., Garcea, R., and Pani, P., 1973, Cholesterol and phospholipid composition of mitochondria and microsomes isolated from Morris hepatoma 5123 and rat liver, FEBS Lett. 33:229–232.
Feo, F., Canuto, R.A., Garcea, R., and Gabriel, L., 1975, Effect of cholesterol content on some physical and functional properties of mitochondria isolated from adult rat liver, fetal liver, cholesterol-enriched liver, and hepatomas AH-130, 3924A and 5123, Biochim. Biophys. Acta 413:116–134.
Forman, B. M., Goode, E., Chen, J., Oro, A. E., Bradley, D. J., Perlman, T., Noonan, D. J., Burke, L. T., McMorris, T., Lamph, W. W., Evans, R. M., and Weinberger, C., 1995, Identification of a nuclear receptor that is activated by farnesol metabolites, Cell 81:687–693.
Garcia, A. M., Rowell, C., Ackermann, K., Kowalczyk, J. J., and Lewis, M. D., 1993, Pep-tidomimetic inhibitors of Ras farnesylation and function in whole cells, J. Biol. Chem. 268:18415–18418.
Gelb, M. H., Tamanoi, F., Yokoyama, K., Ghomashchi, E, Esson, K., and Gould, M. N., 1995, The inhibition of protein prenyltransferases by oxygenated metabolites of limonene and perillyl alcohol, Cancer Lett. 91:169–175.
Giannakouros, T., and Magee, A. I., 1993, Protein prenylation and associated modifications, Lipid Modification of Proteins (M. J. Schlesinger, eds.), pp. 136–162, CRC Press, Boca Raton, Florida.
Gibbs, J. B., 1991, Ras C-terminal processing enzymes-new drug targets? Cell 65:1–4.
Gibbs, J. B., 1992, Pharmacologic probes of Ras function, Cancer Biol. 3:383–390.
Gibbs, J. B., Pompliano, D. L., Mosser, S.D., Rands, E., Lingham, R. B., Singh, S. B., Scolnick, E. M., Kohl, N. E., and Oliff, A., 1993, Selective inhibition of farnesyl-protein transferase blocks processing in vivo, J. Biol. Chem. 268:7617–7620.
Gibbs, J. B., Oliff, A., and Kohl, N. E., 1994, Farnesyltransferase inhibitors: Ras research yields a potential cancer therapeutic, Cell 77:175–178.
Glomset, J. A., Gelb, M. H., and Farnsworth, C. C., 1990, Prenyl proteins in eukaryotic cells: a new type of membrane anchor, Trends Biochem. Sci. 15:139–142.
Glomset, J., Gelb, M., and Farnsworth, C., 1992, Geranylgeranylated proteins, Biochem. Soc. Trans. 20:479–484.
Goldfisher, S., and Reddy, J. K., 1984, Peroxisomes (microbodies) in cell pathology, Intl. Rev. Exp. Pathol 26:45–84.
Goldstein, J. L., and Brown, M. S., 1990, Regulation of the mevalonate pathway, Nature 343:425–430.
Goldstein, J. L., Brown, M. S., Stradley, S. J., Reiss, Y., and Gierasch, L. M., 1991, Nonfarnesylated tetrapeptide inhibitors of protein farnesyltransferase, J. Biol. Chem. 266:15575–15578.
Goodman, L. E., Perou, C. M., Fujiama, A., and Tamanoi, F., 1988, Structure and expression of yeast DPR1, a gene essential for the processing and intracellular localization of ras proteins, Yeast 4: 271–281.
Gould, M. N., Moore, C. J., Zhang, R., Wang, B., Kennan, W. S., and Haag, J. D., 1994, Limonene chemoprevention of mammary carcinoma induction following direct in situ transfer of v-Ha-ras, Cancer Res. 54:3540–3543.
Graham, J. M., and Green, C., 1970, The properties of mitochondria enriched in vitro with cholesterol, Eur. J. Biochem. 12:58–66.
Graham, S. L., deSolms, S. J., Giuliani, E. A., Kohl, N. E., Mosser, S. D., Oliff, A. I., Pompliano, D. L., Rands, E., Breslin, M. J., Deana, A. A., Garsky, V. M., Scholz, T. H., Gibbs, J. B., and Smith, R. L., 1994, Pseudopeptide inhibitors of Ras farnesyl-protein transferase, J. Med. Chem. 37:725–732.
Grünler, J., Ericsson, J., and Dallner, G., 1994, Branch-point reactions in the biosynthesis of cholesterol, dolichol, ubiquinone and prenylated proteins, Biochim. Biophys. Acta 1212:259–277.
Guidotti, G., 1972, Membrane proteins, Annu. Rev. Biochem. 41:731–752.
Gupte, S., Wu, E.-S., Hoechli, L., Hoechli, M., Jacobson, K., Sowers, A. E., and Hackenbrock, C. R., 1984, Relationship between lateral diffusion, collisional frequency, and electron transfer of mitochondrial inner membrane oxidation-reduction components, Proc. Natl. Acad. Sci. USA 81: 2606–2610.
Guthrie, N., Nesaretnam, K., Chambers, A. F., and Carroll, K. K., 1993, Inhibition of breast cancer cell growth by tocotrienols, FASEB J. 7:A7.
Gutierrez, L., Magee, A., Marshall, C., and Hancock, J., 1989, Post-translational processing of p21ras is two-step and involves carboxyl-methylation and carboxy-terminal proteolysis, EMBO J. 8:1093–1098.
Haag, J. D., Lindstrom, M. J., and Gould, M. N., 1992, Limonene-induced regression of mammary carcinomas, Cancer Res. 52:4021–4026.
Habenicht, A. J. R., Glomset, J. A., and Ross, R., 1980, Relation of cholesterol and mevalonic acid to the cell cycle in smooth muscle and Swiss 3T3 cells stimulated to divide with platelet-derived growth factor, J. Biol. Chem. 255:5134–5140.
Hackenbrock, C. R., 1981, Lateral diffusion and electron transfer in the mitochondrial inner membrane, Trends Biochem. Sci. 6:151–154.
Hackenbrock, C. R., Schneider, H., Lemasters, J. J., and Hochli, M., 1980, Diffusional activity of redox components related to electron transfer in the mitochondrial energy transducing membrane, EBEC Reports 1:23–24.
Haines, T. H., 1993, Water transport across biological membranes, FEBS Lett. 346:115–122.
Hall, A., 1990, The cellular functions of small GTP-binding proteins, Science 249:635–640.
Hall, A., 1994, A biochemical function for Ras-at last, Science 264:1413–1414.
Hamilton, R. L., Wong, J. S., Guo, L. S., Krisans, S. K., and Havel, R. J., 1990, Apolipoprotein E localization in rat hepatocytes by immunogold labeling of cryo-thin sections, J. Lipid Res. 31: 1589–1604.
Hancock, J. F., Magee, A. I., Childs, J. E., and Marshall, C. J., 1989, All ras proteins are polyiso-prenylated but only some are palmitoylated, Cell 57:1167–1177.
Hancock, J. F., Paterson, H., and Marshall, C. J., 1990, A polybasic domain or palmitoylation is required in addition to the CAAX motif to localize p21-ras to the plasma membrane, Cell 63: 133–139.
Hancock, J. F., Cadwallader, K., and Marshall, C. J., 1991, Methylation and proteolysis are essential for efficient membrane binding of prenylated p21(K-ras(B)), EMBO J. 10:641–646.
Hara, M., Akasaka, K., Akinaga, S., Okabe, M., Nakano, H., Gomez, R., Wood, D., Uh, M., and Tamanoi, F., 1993, Identification of Ras farnesyltransferase inhibitors by microbial screening, Proc. Natl Acad. Sci. USA 90:2281–2285.
Haiti, F.-U., Pfanner, N., Nicholson, D. W., and Neupert, W., 1989, Mitochondrial protein import, Biochim. Biophys. Acta 988:1–45.
Hashimoto, F., Ishikawa, T., Hamada, S., and Hayashi, H., 1995, Effect of gemfibrozil on lipid biosynthesis from acetyl-CoA derived from peroxisomal β-oxidation, Biochem. Pharmacol. 49: 1213–1221.
Hayashi, H., and Miwa, A., 1989, The role of peroxisomal fatty acyl CoA β-oxidation in bile acid synthesis, Arch. Biochem. Biophys. 274:582–589.
Hiatt, R. A., and Fireman, B. H., 1986, Serum cholesterol and the incidence of cancer in a large cohort, J. Chronic Dis. 39:861–870.
Hohl, R. J., and Lewis, K., 1995, Differential effects of monoterpenes and lovastatin on RAS processing, J. Biol. Chem. 270:17508–17512.
Hornbeck, P., Huang, K.-R, and Paul, W., 1988, Lamin B is rapidly phosphorylated in lymphocytes after activation of protein kinase C., Proc. Natl. Acad. Sci. USA 85:2279–2283.
Hudgins, W. R., Shack, S., Myers, C. E., and Samid, D., 1995, Antitumor activity of phenylacetate and derivatives: Correlation with lipophilicity and inhibition of protein prenylation, Biochem. Pharmacol. 50:1273–1279.
Isserman, I., and Green, S., 1990, Activation of a member of the steroid hormone receptor super-family by peroxisome proliferators, Nature 347:645–650.
Jain, M. K., 1975, Role of cholesterol in biomembranes and related systems, in: Curr. Topics Memb. Transport (F. Bronner and A. Kleinzeller, eds.), pp. 1–84, Academic Press, NY.
Jain, M. K., and White, H. B., III, 1977, Long-range order in biomembranes, Adv. Lipid Res. 15:1–60.
Jakobisiak, M., Bruno, S., Skierski, J., and Darzynkiewicz, Z., 1991, Cell cycle-specific effects of lovastatin, Proc. Natl. Acad. Sci. USA 88:3628–3632.
James, G., Goldstein, J. L. and Brown, M. S., 1996, Resistance of K-RasBV12 proteins to farnesyl-transferase inhibitors in Rat 1 cells, Proc. Natl. Acad. Sci. USA 93: 4454–4458.
James, G. L., Goldstein, J. L., Brown, M. S., Rawson, T. E., Somers, T. C., McDowell, R. S., Crowley, C. W., Lucas, B. K., Levinson, A. D., and Marsters, J. C. J., 1993, Benzodiazepine peptidomimetics: potent inhibitors of Ras farnesylation in animal cells, Science 260:1937–1942.
James, G. L., Brown, M. S., Cobb, M. H., and Goldstein, J. L., 1994, Benzodiazepine peptidomimetic BZA-5B interrupts the MAP kinase activation pathway in H-ras transformed Rat-1 cells, but not in untransformed cells, J. Biol. Chem. 269:21105–21114.
James, G. L., Goldstein, J. L., Pathak, R. K., Anderson, R. G. W., and Brown, M. S., 1994, PxF, a prenylated protein of peroxisomes, J. Biol. Chem. 269:14182–14190.
James, G. L., Goldstein, J. L. and Brown, M. S., 1995, Polylysine and CVIM sequences of K-RasB dictate specificity of prenylation and confer resistence to benzodiazepine peptidomimetic in vitro J. Biol. Chem. 270: 6221–6226.
Kandutsch, A. A., and Chen, H. W., 1977, Consequences of blocked sterol synthesis in culture cells: DNA synthesis and membrane composition, J. Biol. Chem. 252:409–415.
Kandutsch, A. A., and Hancock, R. L., 1971, Regulation of the rate of sterol synthesis and the level of β-hydroxy-β-methyglutaryl coenzyme A reductase activity in mouse liver and hepatomas, Cancer Res. 31:1396–1400.
Kandutsch, A. A., Heiniger, H.-J., and Chen, H. W., 1977, Effects of 25-hydroxycholesterol and 7-ketocholesterol inhibitors, Biochim. Biophys. Acta 486:260–272.
Kaplan, R. S., 1996, Mitochondrial transport processes, in: Molecular Biology of Membrane Transport Disorders (S. G. Schultz, T. Andreoli, A. Brown et al., eds.), pp. 277–302, Plenum Press, NY.
Kaplan, R. S., Mayor, J. A., Johnston, N., and Oliveira, D. L., 1990, Purification and characterization of the reconstitutively active tricarboxylate transporter from rat liver, J. Biol. Chem. 265: 13379–13385.
Kaplan, R. S., and Mayor, J. A., 1993, Structure, function and regulation of the tricarboxylate transport protein from rat liver mitochondria, J. Bioener. Biomemb. 25:503–514.
Kaplan, R. S., Mayor, J. A., and Wood, D. O., 1993, The mitochondrial tricarboxylate transport protein. cDNA cloning, primary structure, and comparison with other mitochondrial transport proteins, J. Biol. Chem. 268:13682–13690.
Kaplan, R. S., Parlo, R. A., and Coleman, P. S., 1986, Measurement of citrate transport in tumor mitochondria, Meth. Enzymol. 125:671–691.
Kaplan, R. S., Morris, H. P., and Coleman, P. S., 1982, Kinetic characteristics of citrate influx and efflux with mitochondria from Morris hepatomas 3924A and 16, Cancer Res. 42:4399–4407.
Kaschnitz, R. M., Morris, H. P., and Hatefi, Y., 1976, Oxidative phosphorylation properties of mito-chondria isolated from transplanted hepatoma, Biochim. Biophys. Acta 449:224–235.
Kawai, S., Yahata, N., Nishida, S., Nagai, K., and Mizushima, Y., 1995, Dehydroepiandrosterone inhibits B16 mouse melanoma cell growth by induction of differentiation, Anticancer Res. 15:427–431.
Keller, G.-A., Barton, M. C., Shapiro, D. J., and Singer, S. J., 1985, 3-Hydroxy-3-methylglutaryl coenzyme A reductase is present in peroxisomes in normal rat liver cells, Proc. Natl. Acad. Sci. USA 82:770–774.
Keller, G.-A., Cable, S., El Bouhtoury, F., Heusser, S., Scotto, C., Armbruster, L., Ciolek, E., Colin, S., Schilt, J., and DauAa, M., 1993, Peroxisomes through cell differentiation and neoplasia, Biol. Cell 77:77–88.
Keyomarsi, K., Sandoval, L., Band, V., and Pardee, A. B., 1991, Synchronization of tumor and normal cells from G1 to multiple cell cycles by lovastatin, Cancer Res. 51:3602–3609.
Keys, A., Aravanis, C., Blackburn, H., Buzina, R., Dontas, A. S., Fidanza, F., Karvonen, M. J., Menotti, A., Nedeljkovic, S., and Punsar, S., 1985, Serum cholesterol and cancer mortality in the Seven Countries study, Am. J. Epidemiol. 121:870–883.
Khosravi-Far, R., Lutz, R. J., Cox, A. D., Conroy, L., Bournes, J. R., Sinensky, M., Balch, W. E., Buss, J. E., and Der, C. J., 1991, Isoprenoid modification of rab proteins terminating in CC or CXC motifs, Proc Natl Acad. Sci. USA 88:6264–6268.
Khosravi-Far, R., Clark, G. J., Abe, K., Cox, A. D., McLain, T., Lutz, R. J., Sinensky, M., and Der, C. J., 1992, Ras (CXXX) and Rab (CC/CXC) prenylation signal sequences are unique and functionally distinct, J. Biol. Chem. 267:24363–24368.
Kinsella, B., and Maltese, W., 1992, rab GTP-binding proteins with three different carboxyl-terminal cysteine motifs are modified in vivo by 20-carbon isoprenoids, J. Biol. Chem. 267:3940–3945.
Knekt, P., Reunanen, A., Aromaa, A., Heliovaara, M., Hakulinen, T., and Hakama, M., 1988, Serum cholesterol and risk of cancer in a cohort of 39,000 men and women, J. Clin. Epidemiol. 41:519–530.
Kohl, N., Diehl, R., Shaber, M., Rands, E., Soderman, D., He, B., Moores, S., Pompliano, D., Ferro-Novick, S., Powers, S., Thomas, K., and Gibbs, J. B., 1991, Structural homology among mammalian and Saccharomyces cerevisiae isoprenyl-protein transferases, J. Biol. Chem. 266: 18884–18888.
Kohl, N. E., Mosser, S. D., deSolms, J., Guiliani, E. A., Pompliano, D. L., Graham, S. L., Smith, R. L., Scolnick, E. M., Oliff, A., and Gibbs, J. B., 1993, Selective inhibition of ras-dependent transformation by a farneslytransferase inhibitor, Science 260:1937–1943.
Kohl, N. E., Wilson, F. R., Mosser, S. D., Giuliani, E. A., deSolmes, S. J., Conner, M. W., Anthony, M. J., Holtz, W. J., Gomez, R. P., Lee, T.-J., Smith, R. L., Graham, S. L., Hart-man, G. D., Gibbs, J. B., and Oliff, A., 1994, Protein farnesyl transferase inhibitors block the growth of ras-dependent tumors in nude mice, Proc. Natl. Acad. Sci. USA 91: 9141–9145.
Kohl, N. E., Omer, C. A., Conner, M. W., Anthony, N. J., Davide, J. P., deSolms, S. J., Guiliani, W. A., Gomez, R. P., Graham, S. L., Hamilton, K., Handt, L. K., Hartman, G. D., Koblan, K. S., Kral, A. M., Miller, P. J., Mosser, S. D., O’Neill, T. J., Rands, E., Schaber, M. D., Gibbs, J. B., and Oliff, A., 1995, Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice, Nature Medicine 1:792–797.
Komiyama, K., Lizuka, K., Yamaoka, M., Watanabe, H., Tsuchiya, N., and Umezawa, I., 1989, Studies on the biological activity of tocotrienols, Chem. Pharm. Bull. 37:1369–1371.
Komori, A., Suganuma, M., Okabe, S., Zou, X., Tius, M. A., and Fujuki, H., 1993, Caventrol inhibits tumor promotion in CD-1 mouse skin through inhibition of tumor necrosis factor α release and protein isoprenylation, Cancer Res. 53:3462–3464.
Kothapalli, R., Guthrie, N., Chambers, A. F., and Carroll, K. K., 1993, Farnesylamine: an inhibitor or farnesylation and growth of ras-transformed cells, Lipids 28:969–973.
Krämer, R., 1982, Cholesterol as activator of ADP-ATP exchange in reconstituted liposomes and in mitochondria, Biochim. Biophys. Acta 693:296–304.
Krisans, S. K., 1992, The role of peroxisomes in cholesterol metabolism, Am. J. Respir. Cell Mol. Biol. 7:358–364.
Krisans, S. K., 1996, Cell compartmentalization of cholesterol biosynthesis, in: Peroxisomes: Biology and Role in Toxicology and Disease (J. K. Reddy, T. Suga, G. P. Mannaerts, S. Subramani, and P. B. Lazerow, eds.) Annals New York Acad. Sci. 804: 142–164.
Krisans, S. K., Motensen, R. M., and Lazarow, P. B., 1980, Acyl CoA synthetase in rat liver peroxisomes: computer-assisted analysis of cell fractionation experiments, J. Biol. Chem. 255: 9599–9607.
Krisans, S. K., Rusnak, N., Keller, G.-A., and Edwards, P. A., 1988, Localization of 3-hydroxy-3-methylglutaryl coenzyme A synthase in rat liver peroxisomes, J. Cell Biol. 107:122a.
Krisans, S. K., Ericsson, J., Edwards, P. A., and Keller, G. A., 1994, Farnesyl-diphosphate synthase is localized in peroxisomes, J. Biol. Chem. 269:14165–14169.
Kromhout, D., Bosschieter, E. B., Dreijver, M., and de Lezenne Coulander, C., 1988, Serum cholesterol and 25-year incidence of and mortality from myocardial infarction and cancer: the Zutphen study, Arch. Intern. Med. 148:1051–1055.
Kuroda, Y., Suzuki, N., and Kataoka, T., 1993, The effect of posttranslational modifications on the interaction of Ras2 with adenylyl cyclase, Science 259:683–686.
Langan, T. J., and Volpe, J. J., 1987, Cell cycle-specific requirement for mavalonate, but not for cholesterol, for DNA synthesis in glial primary cultures, J. Neurochem. 49:513–521.
Langan, T. J., and Volpe, J. J., 1987, Oligodendroglial differentiation in glial primary cultures: requirement for mevalonate, J. Neurochem. 48:1804–1808.
Lange, Y., 1992, Tracking cell cholesterol with cholesterol oxidase, J. Lipid Res. 33:315–321.
Lange, Y., Swaisgood, M. H., Ramos, B. V., and Steck, T. L., 1989, Plasma membranes contain half the phospholipid and 90% of the cholesterol and sphingomyelin in cultured human fibroblasts, J. Biol. Chem. 264:3786–3793.
LaNoue, K. F., and Schoolwerth, A. C., 1979, Metabolite transport in mitochondria, Annu. Rev. Biochem. 48:871–922.
LaNoue, K. F., and Schoolwerth, A. C., 1984, Metabolite transport in mammmalian mitochondria, in: Bioenergetics (L. Ernster, ed.), pp. 221–268, Elsevier, NY
Lardy, H., Partridge, B., and Wei, Y., 1995, Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone, Proc. Natl. Acad. Sci. USA 92: 6617–6619.
Lavietes, B., and Coleman, P. S., 1980, The role of lipid metabolism in neoplastic differentiation, J. Theor. Biol. 85:523–542.
Leevers, S. J., Paterson, H. F., and Marshall, C. J., 1994, Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane, Nature 369:411–414.
Leftheris, K., Kline, T., Vite, G. D., Cho, Y H., Bhide, R. S., Patel, D. V., Patel, M. M., Schmidt, R. J., Weller, H. N., Andahazy, M. L., Carboni, J. M., Gullo-Brown, J. L., Lee, F. Y., Ricca, C., Rose, W. C., Yan, N., Barbacid, M., Hunt, J. T., Meyers, C. A., Seizinger, B. R., Zahler, R., and Manne, V., 1996, Development of highly potent inhibitors of Ras farensyltransferase possessing cellular and in vivo activity, J. Med. Chem. 39: 224–236.
Leonard, S., Beck, L., and Sinensky, M., 1990, Inhibition of isoprenoid biosynthesis and the post-translatinal modification of pro-p21ras, J. Biol. Chem. 265:5157–5160.
Lerner, E. C., Qian, Y., Hamilton, A. D., and Sebti, S. M., 1996, Disruption of oncogenic K-Ras4B processing and signaling by a potent geranylgeranyltransferase I inhibitor J. Biol. Chem. 270: 26770–26773.
Lin, D., Sugawara, T., Strauss III, J. F., Clark, B. J., Stocco, D. M., Saenger, P., Rogol, A., and Miller, W. L., 1995, Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis, Science 267:1828–1831.
Liscum, L., and Dahl, N. K., 1992, Intracellular cholesterol transport, J. Lipid Res. 33:1239–1254.
Liscum, L., and Underwood, K. W., 1995, Intracellular cholesterol transport and compartmentation, J. Biol. Chem. 270:15443–15446.
Liu, W. C., Barbacid, M., Bulgar, M., Clark, J. M., Crosswell, A. R., Dean, L., Doyle, T. W., Fernandes, P. B., Huang, S., Manne, V., Pirnik, D. M., Wells, J. S., and Meyers, E., 1992, 10′-desmethoxystreptonigrin, a novel analog of streptonigrin, J. Antibiot. 45:454–457.
Liu, L., Shack, S., Stetler-Stevenson, W., Hudgins, W. R., and Samid, D., 1994, Differentiation of cultured human melanoma cells induced by the aromatic fatty acids phenylacetate and phenyl-butyrate, J. Invest. Dermatol 103:335–340.
Liu, L., Hudgins, W. R., Shack, S., Yin, M. Q., and Samid, D., 1995, Cinnamic acid: a natural product with potential use in cancer intervention, Int. J. Cancer 62:345–350.
Maltese, W. A., 1990, Posttranslational modification of proteins by isoprenoids in mammalian cells, FASEB J. 4:3319–3328.
Maltese, W. A., and Aprille, J. R., 1985, Relation of mevalonate synthesis to mitochondrial ubiquinone content and respiratory function in cultured neuroblastoma cells, J. Biol. Chem. 260: 11524–11529.
Maltese, W. A., and Sheridan, K. M., 1987, Isoprenylated proteins in cultured cells: subcellular distribution and changes related to altered morphology and growth arrest induced by mevalonate deprivation, J. Cell Physiol 133:471–481.
Maltese, W. A., and Sheridan, K. M., 1988, Isoprenoid synthesis during the cell cycle, J. Biol. Chem. 263:10104–10110.
Maltese, W. A., and Sheridan, K. M., 1988, Studies of 3-hydroxy-3-methylglutaryl coenzyme A synth-ease and reductase and isoprenoid labeling in cells synchronized by centrifugal elutriation, J. Biol Chem. 263:10104–10110.
Maltese, W. A., Defendi, R., Green, R. A., Sheridan, K. M., and Donley, D. K., 1985, Suppression of murine neuroblastoma growth in vivo by mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, J. Clin. Invest. 76:1748–1754.
Manne, V., Yan, N., Carboni, J. M., Tuomari, A. V., Ricca, C. S., Brown, J. G., Andahazy, M. L., Schmidt, R. J., Patel, D., Zahler, R., Weinmann, R., Der, C. J., Cox, A. D., Hunt, J. T., Gordon, E. M., Barbacid, M., and Seizinger, B. R., 1995, Bisubstrate inhibitors of farnesyltransferase: a novel class of specific inhibitors of ras transformed cells, Oncogenes 10:1763–1779.
Marom, M., Haklai, R., Ben-Baruch, G., Marciano, D., Egozi, Y., and Kloog, Y., 1995, Selective inhibition of Ras-dependent cell growth by farnesylthiosalicylic acid, J. Biol. Chem. 270: 22263–22270.
Marshall, C. J., 1993, Protein prenylation: a mediator of protein-protein interactions, Science 259:1865–1866.
Marshall, C. J., 1995, Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation, Cell 80:179–185.
Marshall, M. S., 1993, The effector interactions of p21ras, Trends Biochem. Sci. 18:250–254.
Marsters, J. C. J., McDowell, R. S., Reynolds, M. E., Oare, D. A., Somers, T. C., Stanley, M. S., Raw-son, T. E., Struble, M. E., Burdick, D. J., and Chan, K. S., 1994, Benzodiazepine peptidomimetic inhibition of farnesyltransferase, Bioorg. Med. Chem. 2:949–957.
Martinez, F., Eschegoyen, S., Briones, R., and Cuellar, A., 1988, Cholesterol increase in mitochondria: a new method of cholesterol incorporation, J. Lipid Res. 29:1005–1011.
Maxwell, R. E., Nawrocki, J. W., and Uhlendorf, P. D., 1983, Some comparative effects of gemfibrozil, Clofibrate, bezafibrate, cholestyramine and compactin on sterol metabolism in rats, Atherosclerosis 48:195–203.
McGeady, P., Kuroda, S., Shimizu, K., Takai, Y., and Gelb, M. H., 1995, The farnesyl group of H-Ras facilitates the activation of a soluble upstream activator of mitogen-activated protein kinase, J. Biol. Chem. 270:26347–26351.
Medema, R. H., and Bos, J. L., 1993, The role of p21ras in receptor tyrosine kinase signaling, Crit. Rev. Oncogenesis 4:15–61.
Meigs, T. E., Sherwood, S. W., and Simoni, R. D., 1995, Farnesyl acetate, a derivative of an isoprenoid of the mevalonate pathway, inhibits DNA replication in hamster and human cells, Exp. Cell Res. 219:461–470.
Middleton, A., Middleton, B., White, D. A., and Bell, G. D., 1979, The effects of monocyclic ter-penes on hepatic S-3-hydroxy-3-methylglutaryl coenzyme A reductase in vivo, Biochem. Soc. Trans. 7:407–408.
Miller, A. C., and Samid, D., 1994, Tumor resistance to oxidative stress: association with ras oncogene expression and reversal by lovastatin, an inhibitor of P21 ras isoprenylation, Int. J. Cancer 59:1–6.
Miller, A. C., Kariko, K., Myers, C. E., Clark, E. P., and Samid, D., 1993, Increased radioresistance of EJras-transformed human osteosarcoma cells and its modulation by lovastatin, an inhibitor of p21 ras isoprenylation, Int. J. Cancer 53:302–307.
Miura, S., Hasumi, K., and Endo, A., 1993, Inhibition of protein prenylation by patulin, FEBS Lett. 318:88–90.
Montgomery, R. B., Moscatello, D. K., Wong, A. J., Cooper, J. A., and Stahl, W. L., 1995, Differential modulation of mitogen-activated protein (MAP) kinase/extracellular signal-related kinase kinase and MAP kinase activities by a mutant epidermal growth factor receptor, J. Biol. Chem. 270: 30562–30566.
Moomaw, J., and Casey, P., 1992, Mammalian protein geranylgeranyltransferase, J. Biol. Chem. 267: 17438–17443.
Moores, S. L., Schaber, M., Mosser, S., Rands, E., O’Hara, M., Garsky, V., Marshall, M., Pompli-ano, D., and Gibbs, J., 1991, Sequence dependence of protein isoprenylation, J. Biol. Chem. 266:14603–14610.
Moreadith, R. W., and Lehninger, A. L., 1984, The pathways of glutamate and glutamine oxidation by tumor cell mitochondria, J. Biol. Chem. 259:6215–6221.
Mortensen, P. B., Kristensen, S. D., Bloch, A., Jacobsen, B. A., and Rasmussen, S. N., 1988, Diagnostic value of ascitic fluid cholesterol levels in the prediction of malignancy, Scand. J. Gastroenterol. 23:1085–1088.
Morton, R., Cunningham, C., Jester, R., Waite, M., Miller, N., and Morris, H. P., 1976, Alteration of mitochondrial function and lipid composition in Morris 7777 hepatoma, Cancer Res. 36: 3246–3254.
Nagasu, T., Yoshimatsu, K., Rowell, C., Lewis, M. D., and Garcia, A. M., 1995, Inhibition of human tumor xenograft growth by treatment with farnesyl transferase inhibitor B956, Cancer Res. 55:5310–5314.
Nave, J.-E, d’Orchymont, H., Ducep, J.-B., Piriou, F., and Jung, M., 1985, Mechanism of the inhibition of cholesterol biosynthesis by 6-fluoromevalonate, Biochem. J. 227:247–254
Nestler, J. E., Takagi, K., and Strauss III, J. F., 1990, Lipoprotein and cholesterol metabolism in cells that synthesize steroid hormones, in: Advances in Cholesterol Research (M. Esfahani and J. Swaney, eds.), pp. 133–169, Telford Press, Caldwell, NJ.
Newman, C. M. H., and Magee, A. I., 1993, Posttranslational processing of the ras superfamily of small GTP-binding proteins, Biochim. Biophys. Acta 1155:79–96.
Nigam, M., Seong, C.-M., Qian, Y., Hamiton, A. D., and Sebti, S. M., 1993, Potent inhibition of human tumor p21ras farnesyltransferase by A1A2-lacking p21ras CA1 A2X peptidomimetics, J. Biol. Chem. 269:20695–20698.
Nigg, E. A., Kitten, G. T., and Vorburger, K., 1992, Targeting lamin proteins to the nuclear envelope: the role of CaaX box modifications, Biochem. Soc. Trans. 20:500–504.
Norbury, C., and Nurse, P., 1992, Animal cell cycles and their control., Annu. Rev. Biochem. 61: 441–470.
Okwu, A. K., Xu, X.-X., Shiratori, Y., and Tabas, I., 1994, Regulation of the threshold for lipoprotein-induced acyl-CoAxholesterol O-acyltransferase stimulation in macrophages by cellular sphingomyelin content, J. Lipid Res. 35:644–655.
Omer, C.A., Kral, A.M., Diehl, R.E., Prendergast, G.C., Powers, S., Allen, CM., Gibbs, J.B., and Kohl, N.E., 1993, Characterization of recombinant human farnesyl-protein transferase: cloning, expression, farnesyl diphosphate binding and functional homology with yeast prenyl-protein transferases, Biochemistry 32:5167–5176.
Omura, S., van der Pyl, D., Inokoshi, J., and Takashima, H., 1993, Pepticinnamins, new farnesyl-protein tranferase inhibitors produced by an actinomycete. I. Producing strain, fermentation, isolation and biological activity, J. Antibiot. 46:222–228.
Op den Kamp, J. A. F., 1979, Lipid asymmetry in membranes, Annu. Rev. Biochem. 48:47–71.
Pani, P., Canuto, R., Garcea, R., and Feo, F., 1973, Lipid composition of subcellular particles isolated from rat liver and tumor cells, Biochem. Soc. Trans. 1:972–976.
Pardee, A. B., 1989, G1 events and regulation of cell proliferation, Science 246:603–608.
Parker, R. A., Pearce, B. C., Clark, R. W., Gordon, D. A., and Wright, J. J. K., 1993, Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, J. Biol. Chem. 268:11230–11238.
Parlo, R. A., and Coleman, P. S., 1984, Enhanced rate of citrate export from cholesterol-rich hepatoma mitochondria, J. Biol. Chem. 259:9997–10003.
Parlo, R. A., and Coleman, P. S., 1986, Continuous pyruvate carbon flux to newly synthesized cholesterol and the suppressed evolution of pyruvate-generated CO2 in tumors: further evidence for a persistent truncated Krebs cycle in hepatomas, Biochim. Biophys. Acta 886: 169–176.
Patel, D. V., Gordon, E. M., Schmidt, R. J., Weller, H. N., Young, M. G., Zahler, R., Barbacid, M., Carboni, J. M., Gullo-Brown, J. L., Hunihan, L., Ricca, C., Robinson, S., Seizinger, B. R., Tuomari, A. V., and Manne, V., 1995, Phosphinyl acid-based bisubstrate analog inhibitors of Ras farnesyl protein transferase, J. Med. Chem. 38:435–442.
Pearce, B. C., Parker, R. A., Deason, M. E., Qureshi, A. A., and Wright, J. J. K., 1992, Hypocholes-terolemic activity of synthetic and natural tocotrienols, J. Med. Chem. 35:3595–3606.
Pearce, B. C., Parker, R. A., Deason, M. E., Dischino, D. D., Gillespie, E., Qureshi, A. A., Volk, K., and Wright, J. J. K., 1994, Inhibitors of cholesterol biosynthesis. 2. Hypocholesterolemic and antioxidant activities of benzopyran and tetrahydronaphthalene analogues of the tocotrienols, J. Med. Chem. 37:526–541.
Pedersen, P. L., 1978, Tumor mitochondria and the bioenergetics of cancer cells, in: Prog. Exp. Tumor Res. (D. F. H. Wallach, ed.), pp. 190–274, S. Karger, Basel.
Peeper, D. S., van der Eb, A. J., and Zantema, A., 1994, The G1/S cell-cycle checkpoint in eukaryotic cells, Biochim. Biophys. Acta 1198:215–230.
Perez-Sala, D., and Mollinedo, F., 1994, Inhibition of isoprenoid biosynthesis induces apoptosis in human promyelocytic HL-60 cells, Biochem. Biophys. Res. Commun. 199:1209–1215.
Perkins, S. L., Ledin, S. F., and Stubbs, J. D., 1982, Linkage of the isoprenoid biosynthetic pathway with induction of DNA synthesis in mouse lymphocytes. Effects of compactin on mitogen-induced lymphocytes in serum-free medium, Biochim. Biophys. Acta 711:83–89.
Pompliano, D., Rands, E., Schaber, M., Mosser, S., Anthony, N., and Gibbs, J., 1992, Steady-state kinetic mechanism of Ras farnesyl:protein transferase, Biochemistry 31:3800–3807.
Powers, S., Michaelis, S., Broek, D., S., A.-A., Field, J., Herskowitz, I., and Wigler, M., 1986, RAM, a gene of yeast required for a functional modification of RAS proteins and for production of mating pheromone a-factor, Cell 47:413–422.
Prager, C., Schön, H. J., Nikfardjam, M., Schmid, D., Untersalmberger, M., Kremser, K., and Kramar, R., 1993, Clofibrate elevates enzyme activities of the tricarboxylic acid cycle in rat liver, J. Lipid Res. 34:359–364.
Prendergast, G.C., and Gibbs, J. B., 1994, Ras regulatory interactions: Novel targets for anti-cancer intervention?, BioEssays 16:187–191.
Prendergast, G. C., Davide, J. P., deSolms, S. J., Giuliani, E. A., Graham, S. L., Gibbs, J. B., Oliff, A., and Kohl, N. E., 1994, Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechansim that involves regulation of the actin cytoskeleton, Mol Cell Biol. 14:4193–4202.
Privalle, C. T., Crivello, J. F., and Jefcoate, C. R., 1983, Regulation of intramitochondrial cholesterol transfer to side-chain cleavage cytochrome P-450 in rat adrenal gland, Proc. Natl. Acad. Sci. USA 80:702–706.
Qian, Y., Blaskovich, M. A., Saleem, M., Seong, C.-M., Wathen, S. P., Hamilton, A. D., and Sebti, S. M., 1994, Design and structural requirements of potent peptidomimetic inhibitors of p21ras farnesyltransferase, J. Biol. Chem. 269:12410–12413.
Quesney-Huneeus, V., Wiley, M. H., and Siperstein, M. D., 1979, Essential role for mevalonate synthesis in DNA replication, Proc. Natl Acad. Sci. USA 76:5056–5060.
Quesney-Huneeus, V., Galick, H. A., Siperstein, M. D., Erickson, S. K., Spencer, T. A., and Nelson, J. A., 1983, The dual role of mevalonate in the cell cycle, J. Biol. Chem. 258:378–385.
Quilliam, L. A., Huff, S. Y., Rabun, K. M., Wei, W., Park, W., Broek, D., and Der, C. J., 1994, Membrane-targeting potentiates guanine nucleotide exchange factor CDC25 and SOS1 activation of Ras transforming activity, Proc. Natl. Acad. Sci. USA 91:8512–8516.
Qureshi, A. A., Mangels, A. R., Din, Z. Z., and Elson, C. E., 1988, Inhibition of hepatic mevalonate biosynthesis by the monoterpene, D-limonene., J. Agric. Food Chem. 36:1220–1224.
Ram, Z., Samid, D., Walbridge, S., Oshiro, E. M., Viola, J. J., Tao-Cheng, J.-H., Shack, S., Thibault, A., Meyers, C. E., and Oldfield, E. H., 1994, Growth inhibition, tumor maturation, and extended survival in experimental brain tumors in rats treated with phenylacetate, Cancer Res. 54: 2923–2927.
Rao, K. N., 1995, The significance of the cholesterol biosynthetic pathway in cell growth and carcinogenesis, Anticancer Res. 15:309–314.
Rao, S., and Coleman, P. S., 1989, Control of DNA replication and cell growth by inhibiting the export of mitochondrially derived citrate, Exp. Cell Res. 180:341–352.
Reardon, J. E., and Abeles, R. H., 1987, Inhibition of cholesterol biosynthesis by fluorinated mevalonate analogues, Biochemistry 26:4717–4722.
Reddy, J. K., and Lalwani, N. D., 1983, Carcinogenesis by hepatic peroxisome proliferators: evaluation of the risk of hypolipidemic drugs and industrial plasticizers to humans, Crit. Res. Toxicol 12:1–58.
Reddy, J. K., and Mannaerts, G. P., 1994, Peroxisomal lipid metabolism, Annu. Rev. Nutr. 14:343–370.
Regelson, W., and Kalimi, M., 1994, Dehydroepiandrosterone (DHEA)—the multifunctional steroid. II. Effects on the CNS, cell proliferation, metabolic and vascular, clinical and other effects. Mechanism of action? Ann. NY Acad. Sci. 719:564–575.
Reiss, Y., Goldstein, J. L., Seabra, M. C., Casey, P. J., and Brown, M. S., 1990, Inhibition of purified p21ras farnesyliprotein transferase by Cys-AAX tetrapeptides, Cell 62:81–88.
Reiss, Y., Seabra, M., Armstrong, S., Slaughter, C., Goldstein, J., and Brown, M., 1991, Non-identical subunits of p21ras farnesyltransferase: peptide binding and farnesyl pyrophosphate carrier functions, J. Biol. Chem. 266:10672–10677.
Reiss, Y., Stradley, S., Gierasch, L. M., Brown, M. S., and Goldstein, J. L., 1991, Sequence requirement for peptide recognition by rat brain p21ras protein farnesyltransferase, Proc. Natl. Acad. Sci. USA 88:732–736.
Reiss, Y., Brown, M. S., and Goldstein, J. L., 1992, Divalent cation and prenyl pyrophosphate specificities of the protein farnesyltransferase from rat brain, a zinc metalloenzyme, J. Biol. Chem. 267:6404–6408.
Ridley, A. J., and Hall, A., 1992, The small GTP binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors, Cell 70:389–399.
Rilling, H. C., Bruenger, E., Epstein, W. W., and Crain, P. F., 1990, Prenylated proteins: the structure of the isoprenoid group, Science 247:318–320.
Rosen, N., 1995, Oncogenes, in: The Molecular Basis of Cancer (J. Mendelsohn, P. M. Howley, M. A. Israel, and L. A. Liotta, eds.), pp. 105–116, W. B. Saunders Company, Philadelphia.
Rothblat, G. H., Mahlberg, F.H., Johnson, W. J., and Phillips, M. C., 1992, Apolipoproteins, membrane cholesterol domains and the regulation of cholesterol efflux, J. Lipid Res. 33: 1091–1097.
Roussillon, S., Astruc, M., Defay, R., Tabacik, C., Descomps, B., and Crastes de Paulet, A., 1983, DNA and cholesterol biosynthesis in synchronized embryonic rat fibroblasts. Temporal relationships between HMG-CoA reductase activity, sterol biosynthesis and thymidine incorporation into DNA, Biochim. Biophys. Acta 763:1–10.
Ruch, R. J., and Sigler, K., 1994, Growth inhibition of rat liver epithelial tumor cells by monoterpenes does not involve Ras plasma membrane association, Carcinogenesis 15:787–789.
Ruderman, J. V., 1993, MAP kinase and the activation of quiescent cells, Curr. Opin. Cell Biol. 5: 207–213.
Rudney, H., and Sexton, R. C., 1986, Regulation of cholesterol biosynthesis, Annu. Rev. Nutr. 6: 245–272.
Rusnak, N., and Krisans, S. K., 1987, Diurnal variation of HMG-CoA reductase activity in rat liver peroxisomes, Biochem. Biophys. Res. Commun. 148:890–896.
Sabine, J. R., 1975, Defective control of lipid biosynthesis in cancerous and precancerous liver, Prog. Biochem. Pharmacol. 10:269–307.
Samid, D., Miller, A. C., Rimoldi, D., Gafner, J., and Clark, E. P., 1991, Increased radiation resistance in transformed and non-transformed cells with elevated ras proto-oncogene expression, Rad. Res. 126:244–250.
Samid, D., Shack, S., and Sherman, L. T., 1992a, Phenylacetate: a novel nontoxic inducer of tumor cell differentiation, Cancer Res. 52:1988–1992.
Samid, D., Yeh, A., and Prasanna, P., 1992b, Induction of erythroid differentiation and fetal hemoglobin production in human leukemic cells treated with phenylacetate, Blood 80: 1576–1581.
Samid, D., Shack, S., and Meyers, C. E., 1993, Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate, J. Clin. Invest. 91:2288–2295.
Samid, D., Ram, Z., Hudgins, W. R., Shack, S., Liu, L., Walbridge, S., Oldfield, E. H., and Myers, C. E., 1994, Selective activity of phenylacetate against malignant gliomas: resemblance to fetal brain damage in phenylketonuria, Cancer Res. 54:891–895.
Sanford, J. C., Foster, L., Kapadia, Z., and Wessling-Resnick, M., 1995, Analysis of the stoichiometry of Rab protein prenylation, Anal. Biochem. 224:547–556.
Sapperstein, S., Berkower, C., and Michaelis, S., 1994, Nucleotide sequence of the yeast STE14 gene which encodes an isoprenylcysteine carboxyl methyltransferase and demonstration of its essential role in a-factor export, Mol. Cell Biol. 14:1438–1449.
Sawamura, M., Li, N., Nara, Y., and Yamori, Y., 1993, Proliferative effect of mevalonate metabolites other than isoprenoids on cultured vascular smooth muscle cells, Clin. Exp. Pharm. Physiol. 20: 509–514.
Schafer, W. R., and Rine, J., 1992, Protein prenylation: genes enzymes, targets and functions, Annu. Rev. Genet. 26:209–237.
Schatzkin, A., Hoover, R. N., Taylor, P. R., Zeigler, R. G., Carter, C. L., Albanes, D., Larson, D. B., and Licitra, L. M., 1988, Site-specific analysis of total serum cholesterol and incident cancer in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study, Cancer Res. 48:452–458.
Schepers, L., Casteels, M., Vamecq, J., Parmentier, G., van Veldhoven, P. P., and Mannaerts, G. P., 1988, β-Oxidation of the carboxyl side-chain of prostaglandin E2 in rat liver peroxisomes and mitochondria, J. Biol. Chem. 263:2724–2731.
Schepers, L., van Veldhoven, P. P., Casteels, M., Eyssen, H., and Mannaerts, G. P., 1990, Presence of three acyl-CoA oxidases in rat liver peroxisomes, J. Biol. Chem. 265:5242–5246.
Schmidt, R. A., Schneider, C. L., and Glomset, J. A., 1984, Evidence for post-translational incorporation of a product of mevalonic acid into Swiss 3T3 cell proteins, J. Biol. Chem. 259:10175–10180.
Schneider, H., Lemasters, J. J., Höchli, M., and Hackenbrock, C. R., 1980, Fusion of liposomes with mitochondrial inner membranes, Proc. Natl. Acad. Sci. USA 77:442–446.
Schneider, H., Lemasters, J. J., Höchli, M., and Hackenbrock, C. R., 1980, Liposome-mitochondrial inner membrane fusion, J. Biol. Chem. 255:3748–3756.
Schneider, H., Höchli, M., and Hackenbrock, C. R., 1982, Relationship between the density distribution of intramembrane particles and electron transfer in the mitochondrial inner membrane as revealed by cholesterol incorporation, J. Cell Biol. 94:387–393.
Schultz, S., and Nyce, J. W., 1991, Inhibition of protein isoprenylation and p21ras membrane association by dehydroepiandrosterone in human colonic adenocarcinoma cells in vitro, Cancer Res. 51:6563–6567.
Schultz, S., Klann, R. C., Schonfeld, S., and Nyce, J. W., 1992, Mechanisms of cell growth inhibition and cell cycle arrest in human colonic adenocarcinoma cells by dehydroepiandrosterone: role of isoprenoid biosynthesis, Cancer Res. 52:1372–1376.
Schwartz, A. G., Whitcomb, J. M., Nyce, J. W., Lewbart, M. L., and Pashko, L. L., 1988, Dehydroepiandrosterone and structural analogs: a new class of cancer chemopreventive agents, Adv. Cancer Res. 51:391–424.
Seabra, M., Goldstein, J., Sudhof, M., and Brown, M., 1992, Rab geranylgeranyl transferase, J. Biol. Chem. 267:14497–14503.
Sebti, S. M., Tkalavic, G. T., and Jani, J. P., 1991, Lovastatin, a cholesterol biosynthesis inhibitor, inhibits the growth of human H-ras oncogene transformed cells in nude mice, Cancer Commun. 3:141–147.
Seedorf, U., Brysch, P., Engel, T., Schrage, K., and Assmann, G., 1994, Sterol carrier protein X is peroxisomal 3-oxoacyl CoA thiolase with intrinsic sterol carrier and lipid transfer activity, J. Biol. Chem. 269:21277–21283.
Sepp-Lorenzino, L., Azrolan, N. I., and Coleman, P. S., 1989, Cellular distribution of cholesterogenesis-linked, phospho-isoprenylated proteins in proliferating cells, FEBS Lett. 245:110–116.
Sepp-Lorenzino, L., Rao, S., and Coleman, P. S., 1991, Cell-cycle-dependent, differential prenylation of proteins, Eur. J. Biochem. 200:579–590.
Sepp-Lorenzino, L., Coleman, P. S., and Larocca, J., 1994, Isoprenylated proteins in myelin, J. Neu-rochem. 62:1539–1545.
Sepp-Lorenzino, L., Ma, Z., Kohl, N. E., Rands, E., Gibbs, J. B., Oliff, A., and Rosen, N., 1995, A peptidomimetic inhibitor of farnesyl:protein transferase inhibits the anchorage-dependent and-independent growth of human tumor cell lines, Cancer Res. 55:5302–5309.
Shack, S., Chen, L.-C., Miller, A. C., Danesi, R., and Samid, D., 1995, Increased susceptibility of ras-transformed cells to phenylacetate is associated with inhibition of p21ras isoprenylation and phenotypic reversion, Intl. J. Cancer 63:124–129.
Shama Bhat, C., and Ramasarma, T., 1979a, Effect of phenyl and phenolic acids on mevalonate-5-phosphate kinase and mevalonate-5-pyrophosphate decarboxylase of the rat brain, J. Neurochem. 32:1531–1537.
Shama Bhat, C., and Ramasarma, T., 1979b, Inhibition of rat liver mevalonate pyrophosphate decarboxylase and mevalonate phosphate kinase by phenyl and phenolic compounds, Biochem. J. 181:143–151.
Sherwin, R. W., Wentworth, D. N., Cutler, J. A., Hulley, S. B., Kuller, L. H., and Stamler, J., 1987, Serum cholesterol levels and cancer mortality in 361,662 men screened for the Multiple Risk Factor Intervention Trial, JAMA 257:943–948.
Shiomi, K., Yang, H., Inokoshi, J., van der Pyl, D., Nakagawa, A., Takeshima, H., and Omura, S., 1993, Pepticinnamins, new farnesyl-protein tranferase inhibitors produced by an actinomycete. II. Structural elucidation of pepticinnamin E, J. Antibiot. 46:229–234.
Shirataki, H., Kaibuchi, K., Yamaguchi, T., Wada, K., Horiuchi, H., and Takai, Y., 1992, A possible target protein for smg-25A/rab3A small GTP-binding protein, J. Biol. Chem. 267: 10946–10949.
Shu, Y. Z., Huang, S., Wang, R. R., Lam, K. S., Klohr, S. E., Volk, K. J., Pirnik, D. M., Wells, J. S., Fernandes, P. B., and Patel, P. S., 1994, Manumycins E, F, and G, new members of manumycin class antibiotics, from Streptomyces sp., J. Antibiot. 47:324–3
Singh, S. B., Zink, D. L., Liesch, J. M., Goetz, M. A., Jenkins, R. G., Nallin-Olmstead, M., Silverman, K. C., Bills, G. F., Mosley, R. T., Gibbs, J. B., Albers-Schonberg, G., and Lingham, R. B., 1993, Isolation and structure of chaetomellic acids A and B from Chaetomella acutiseta: farnesyl pyrophosphate mimic inhibitos or Ras farnesyl-protein transferase, Tetrahedron 49:5917–5926.
Siperstein, M. D., 1970, Regulation of cholesterol biosynthesis in normal and malignant tissues, in: Current Topics in Cell Regulation (B. L. Horecker and E. R. Stadtman, eds.), pp-65–100, Academic Press, New York.
Siperstein, M. D., 1984, Role of cholesterogenesis and isoprenoid synthesis in DNA replication and cell growth, J. Lipid Res. 25:1462–1468.
Siperstein, M. D., 1995, Cholesterol, cholesterogenesis and cancer, Adv. Exper. Med. Biol. 369: 155–166.
Skalnik, D. G., Brown, D. A., Borwn, P. C., Friedman, R. L., Hardeman, E. C., Schimke, R. T., and Simoni, R. D., 1985, Mechanisms of 3-hydroxy-3-methylglutaryl coenzyme A reductase over-accumulation in three compactin-resistant cell lines, J. Biol. Chem. 260:1991–1994.
Slotte, J. P., Hedström, G., Rannström, S., and Ekman, S., 1989, Effects of sphingomyelin degradation on cell cholesterol oxidizability and steady-state distribution between the cell surface and the cell interior, Biochim. Biophys. Acta 985:90–96.
Smith, M. R., De Gudicibus, S. J., and Stacey, D. W., 1986, Requirement for c-ras proteins during viral oncogene transformation, Nature 320:540–543.
Soldati, T., Shaprio, A. D., Svejstrup, A. B. D., and Pfeffer, S. R., 1994, Membrane targeting of the small GTPase Rab9 is accompanied by nucleotide exchange, Nature 369:76–78.
Spady, D. K., 1991, Regulation of cholesterol metabolism in normal and malignantly transformed tissue in vivo, in: Chemical Carcinogenesis-2: Modulating Factors (A. Columbano, F. Feo, R. Pascale, and P. Pani, eds.), pp. 299–309, Plenum Press, NY.
Spector, A. A., and Yorek, M. A., 1985, Membrane lipid composition and cellular function, J. Lipid Res. 26:1015–1035.
Srere, P., 1975, The enzymology of the formation and breakdown of citrate, Adv. Enzymol. 43:57–101.
Stamellos, K. D., Shackelford, J. E., Tanaka, R. D., and Krisans, S. K., 1992, Mevalonate kinase is localized in rat liver peroxisomes, J. Biol. Chem. 267:5560–5568.
Stamellos, K. D., Shackelford, J. E., Shechter, I., Jiang, G., Conrad, D., Keller, G. A., and Krisans, S. K., 1993, Subcellular localization of squalene synthase in rat hepatic cells. Biochemical and immunochemical evidence, J. Biol. Chem. 268:12825–12836.
Stange, E. F., Preclik, G., Schneider, A., and Reimann, F., 1988, The role of enterocyte cholesterol metabolism in intestinal cell growth and differentiation, Scand. J. Gastroent. 151:79–85.
Stimmel, J. B., Deschenes, R., Volker, C., Stock, J., and Clarke, S., 1990, Evidence for an S-farnesyl-cysteine methyl ester at the carboxyl terminus of the Saccharomyces cerevisiae RAS2 protein, Biochemistry 29:9651–9659.
Stokoe, D., Macdonald, S. G., Cadwallader, K., Symons, M., and Hancock, J. F., 1994, Activation of Raf as a result of recruitment to the plasma membrane, Science 264:1463–1467.
Stradley, S. J., Rizo, J., and Gierasch, L. M., 1993, Conformation of a heptapeptide substrate bound to protein farnesyltransferase, Biochemistry 32:12586–12590.
Sumi, S., Beauchamp, D., Townsend, C. M., Jr., Uchida, T., Murakami, M., Rajaraman, S., Ishizuka, J., and Thompson, J. C., 1992, Inhibition of pancreatic adenocarcinoma cell growth by lovastatin, Gastroenterology 103:982–989.
Tabacik, C., and Aliau, S., 1989, Cholesterogenesis and cell division in phytohemagglutinin-stimulated human lymphocytes: a comparative study with several inhibitors, Biochim. Biophys. Acta 1011: 149–157.
Tamanoi, F., 1993, Inhibitors of Ras farnesyltransferases, Trends Biochem. Sci. 18:349–353.
Tertov, V. V., Orekhov, A. N., Ryong, L. H., and Smirnov, V. N., 1988, Intracellular cholesterol accumulation is accompanied by enhanced proliferative activity of human aortic intimal cells, Tissue Cell. 20:849–854.
Thibault, A., Cooper, M. R., Figg, W. D., Venzon, D. J., Sartor, A. O., Tompkins, A. C., Weinberger, M. S., Headlee, D. J., McCall, N. A., Samid, D., and Meyers, C. E., 1994, A phase I and pharmacokinetic study of intraveous phenylacetate in patients with cancer, Cancer Res. 54: 1690–1694.
Thompson, S. L., and Krisans, S. K., 1990, Rat liver peroxisomes catalyze the initial step in cholesterol synthesis: the condensation of acetyl CoA units into acetoacetyl CoA, J. Biol. Chem. 265: 5731–5735.
Toth, M. J., Park, J., and Huwyler, L., 1995, Purification of rat liver mevalonate pyrophosphate decarboxylase, FASEBJ. 9:A1293.
Trentalance, A., Leoni, S., Mangiantini, M. T., Spagnuolo, S., Feingold, K., Hughes-Fulford, M., Siper-stein, M. D., Cooper, A. D., and Erickson, S. K., 1984, Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol synthesis and esterification during the first cell cycle of liver regeneration, Biochim. Biophys. Acta 794:142–151.
Trueblood, C. E., Ohya, Y., and Rine, J., 1993, Genetic evidence for in vivo cross-specificity of the CaaX-box protein prenyltransferases farnesyltransferase and geranylgeranyltransferase-I in Saccharomyces cerevisiae, Mol Cell Biol. 13:4260–4275.
van Blitterswijk, W. J., Emmelot, P., Hilkmann, H. A. M., Oomenmeulmans, E. P. M., and Inbar, M., 1977, Differences in lipid fluidity among isolated plasma membranes of normal and leukemic lymphocytes and membranes exfoliated from their cell surface, Biochim. Biophys. Acta 467: 309–320.
van Blitterswijk, W. J., Emmelot, P., Hilkmann, H. A. M., Higers, J., and Feltkamp, C. A., 1979, Rigid plasma membrane-derived vesicles, enriched in tumor-associated surface antigens (MLr) occurring in the ascites fluid of a murine leukemia (GRSL), Intl. J. Cancer 23:62–70.
van Blitterswijk, W. J., De Veer, G., Krol, J. H., and Emmelot, P., 1982, Comparative lipid analysis of purified plasma membranes and shed extracellular membrane vesicles from normal murine thymocytes and leukemic GRSL cells, Biochim. Biophys. Acta 688:495–504.
van Blitterswijk, W. J., Hilkmann, H., and Hengeveld, T., 1984, Differences in membrane lipid composition and fluidity of transplanted GRSL lymphoma cells, depending on their site of growth in the mouse, Biochim. Biophys. Acta 778:521–529.
van der Pyl, D., Inokoshi, J., Shiomi, K., Yang, H., Takeshima, H., and Omura, S., 1992, Inhibition of farnesyl:protein transferase by gliotoxin and acetylgliotoxin, J. Antibiot. 45:1802–1805.
van Hoeven, R., and Emmelot, P., 1972, Studies on plasma membranes. XVIII. Lipid class composition of plasma membranes isolated from rat and mouse liver and hepatomas, J. Membr. Biol. 9:105–126.
van Meer, G., 1987, Plasma membrane cholesterol pools, Trends Biochem. Sci. 12:375–376.
Vincent, T., Wulfert, E., and Merler, E., 1991, Inhibition of growth factor signaling pathways by lovastatin, Biochem. Biophys. Res. Commun. 180:1284–1289.
Vogt, A., Qian, Y., Blaskovich, M. A., Fossum, R. D., Hamilton, A. D., and Sebti, S. M., 1995, A non-peptide mimetic of Ras-CAAX: selective inhibition of farnesyltransferase and Ras processing, J. Biol. Chem. 270:660–664.
Waterman, M. R., 1995, A rising StAR: an essential role in cholesterol transport, Science 267: 1780–1781.
Watson, J. A., Havel, C. M., Lobos, D. V., Baker, F. C., and Morrow, C. J., 1985, Isoprenoid synthesis in isolated embryonic Drosophila cells, J. Biol. Chem. 260:14083–14091.
Wedegaertner, P. B., Wilson, P. T., and Bourne, H. R., 1995, Lipid modifications of trimeric G proteins, J. Biol. Chem. 270:503–506.
Weibel, E. R., 1984, The Pathway for Oxygen: Structure and Function in the Mammalian Respiratory System, Harvard University Press, Cambridge, MA.
Willumsen, B. M., Norris, K., Papageorge, A. G., Hubbert, N. L., and Lowy, D. R., 1984, Harvey murine sarcoma virus p21 ras protein: biological and biochemical significance of the cysteine nearest the carboxy terminus, EMBO J. 3:2581–2585.
Wirtz, K. W. A., 1991, Phospholipid transfer proteins, Annu. Rev. Biochem. 60:73–99.
Wittinghofer, A., and Herrmann, C., 1995, Ras-effector interactions, the problem of specificity, FEBS Lett. 369:52–56.
Xu, Y., Mayor, J. A., Gresme, D., Wood, D., and Kaplan, R. S., 1995, High-yield bacterial expression, purification, and functional reconstitution of the tricarboxylate transport protein from rat liver mitochondria, Biochem. Biophys. Res. Commun. 207:783–789.
Yan, N., Ricca, C., Fletcher, J., Glover, T., Seizinger, B. R., and Manne, V., 1995, Farnesyltransferase inhibitors block the neurofibromatosis type I (NFI) malignant phenotype, Cancer Res. 55: 3569–3575.
Yeagle, P., 1987, The Membranes of Cells, Academic Press, NY.
Yeagle, P., 1992, The dynamics of membrane lipids, in: The Structure of Biological Membranes (P. Yeagle, ed.), pp. 157–174, CRC Press, Boca Raton, FL.
Yeagle, P. L., 1991, Modulation of membrane function by cholesterol, Biochimie 73:1303–1310.
Ying, W., Sepp-Lorenzino, L., Cai, K., Aloise, P., and Coleman, P. S., 1994, Photoaffinity-labeling peptide substrates for farnesyl-protein transferase and the intersubunit location of the active site, J. Biol. Chem. 269:470–477.
Yokoyama, K., and Gelb, M. H., 1993, Purification of a mammalian protein geranylgeranyltransferase, J. Biol. Chem. 268:4055–4060.
Yokoyama, K., Goodwin, G., Ghomashchi, F., Glomset, J. A., and Gelb, M., 1991, A protein geranylgeranyltransferase from bovine brain: implications for protein prenylation specificity, Proc. Natl. Acad. Sci. USA 88:5302–5306.
Zafra, M. F., Riquelme, S., Castillo, M., and Garcia-Peregrin, E., 1987, Effect of Clofibrate on brain mevalonate-5-pyrophosphate decarboxylase, Neurochem. Res. 12:787–791.
Zhang, F., and Casey, P. J., 1996, Protein prenylation: molecular mechanisms and functional consequences, Annu. Rev. Biochem. 65:241–269.
Zhang, F. L., Diehl, R. E., Kohl, N. E., Gibbs, J. B., Giros, B., Casey, P. J., and Omer, C. A., 1994a, cDNA cloning and expression of rat and human protein geranylgeranyltransferase type-I, J. Biol. Chem. 269:3175–3180.
Zhang, L., Sachs, C. W., Fine, R. L., and Casey, P. J., 1994b, Interaction of prenylcysteine methyl esters with the multidrug resistance transporter, J. Biol. Chem. 269:15973–15976.
Zhang, L., Sachs, C. W., Fu, H.-W., Fine, R. L., and Casey, P. J., 1995, Characterization of prenylcys-teines that interact with P-glycoprotein and inhibit drug transport in tumor cells, J. Biol. Chem. 270:22859–22865.
Zhang, F. L., Fu, H. W., Casey, P. J., and Bishop, W. R., 1996, Substitution of cadmium for zinc in farnesyl:protein transferase alters its substrate specificity, Biochemistry 35:8166–8171.
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Coleman, P.S., Chen, LC., Sepp-Lorenzino, L. (1997). Cholesterol Metabolism and Tumor Cell Proliferation. In: Bittman, R. (eds) Cholesterol. Subcellular Biochemistry, vol 28. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5901-6_13
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