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Cell Proliferation: From Signal Transduction to Cell Cycle

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Bioprobes

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Abstract

Eukaryotic cells have highly coordinated mechanisms to control cell proliferation. These include mitogenic signaling and cell cycle control. Cells receive a variety of positive and negative signals from external (growth factors, stresses, etc.) and internal (DNA damage, microtubule integrity, etc.) conditions and must decide to start or cease the cell cycle in response to these signals. Malignant cells arise as a result of a stepwise progression of genetic events that include short-circuited signal transduction and unregulated cell cycle progression. This review focuses on several aspects of cell proliferation control and target molecules for bioprobes which are highly useful in exploring the molecular mechanisms of cell proliferation control. Inhibitors of cell proliferation include a variety of classical cytotoxic compounds such as DNA-damaging agents, membrane-attacking agents, macromolecular synthesis inhibitors, and inhibitors of the respiratory system. Although some of these cytotoxic compounds are useful in analyzing cellular functions, this review focuses on relatively recent inhibitors of cell proliferation, of which targets are involved in the regulation of signal transduction and the cell cycle.

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References

  1. Cantley LC, Auger KR, Carpenter C, Duckworth B, Graziani A, Kapeller R, Soltoff S (1991) Oncogenes and signal transduction. Cell 64:281–302

    Article  PubMed  CAS  Google Scholar 

  2. Pawson T (1995) Protein modules and signalling networks. Nature 373:573–580

    Article  PubMed  CAS  Google Scholar 

  3. Vanhaesebroeck B, Leevers SJ, Panayotou G, Waterfiield MD (1997) Phosphoinositide 3-kinases: a conserved family of signal transducers. Trends Biochem Sci 22:267–272

    Article  PubMed  CAS  Google Scholar 

  4. Akimoto K, Takahashi R, Moriya S, Nishioka N, Takayanagi J, Kimura K, Fukui Y, Osada S, Mizuno K, Hirai S, Kazlauskas A, Ohno S (1996) EGF or PDGF receptors activate atypical PKCX through phosphatidylinositol 3-kinase. EMBO J 15:788–798

    PubMed  CAS  Google Scholar 

  5. Fukui Y, Ihara S, Nagata S (1998) Downstream of phosphatidylinositol–3 kinase, a multifunctional signaling molecule, and its regulation in cell responses. J Biochem 124:1–7

    Article  PubMed  CAS  Google Scholar 

  6. Downward J (1998) Mechanisms and consequences of activation of protein kinase B/ Akt. Cuff Opin Cell Biol 10:262–267

    Article  CAS  Google Scholar 

  7. Chung J, Grammer TC, Lemon KP, Kazlauskas A, Blenis J (1994) PDGF- and insulindependent p70s6k activation mediated by phosphatidylinositol-3-OH kinase. Nature 370:71–75

    Article  PubMed  CAS  Google Scholar 

  8. Egan SE, Giddings BW, Brooks MW, Buday L, Sizeland AM, Weinberg RA (1993) Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation. Nature 363:45–51

    Article  PubMed  CAS  Google Scholar 

  9. Buday L, Downward J (1993) Epidermal growth factor regulates p21 ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor. Cell 73:611–620

    Article  PubMed  CAS  Google Scholar 

  10. Darnell JJ, Kerr IM, Stark GR (1994) Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264:1415–1421

    Article  PubMed  CAS  Google Scholar 

  11. Avruch J, Zhang X, Kyriakis JM (1994) Raf meets Ras: completing the framework of a signal transduction pathway. Trends Biochem Sci 19:279–283

    Article  PubMed  CAS  Google Scholar 

  12. Morrison DK, Cutler Jr R (1997) The complexity of Raf-1 regulation. Curr Opin Cell Biol 9:174–179

    Article  PubMed  CAS  Google Scholar 

  13. Vojtek AB, Hollenberg SM, Cooper JA (1993) Mammalian Ras interacts directly with the serine/threonine kinase Raf. Cell 74:205–214

    Article  PubMed  CAS  Google Scholar 

  14. Robinson MJ, Cobb MH (1997) Mitogen-activated protein kinase pathways. Curr Opin Cell Biol 9:180–186

    Article  PubMed  CAS  Google Scholar 

  15. Kyriakis JM, Banerjee P, Nikolakaki E, Dai T, Rubie EA, Ahmad MF, Avruch J, Woodgett JR (1994) The stress-activated protein kinase subfamily of c-Jun kinases. Nature 369:156–160

    Article  PubMed  CAS  Google Scholar 

  16. Han J, Lee JD, Bibbs L, Ulevitch RJ (1994) A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265:808–811

    Article  PubMed  CAS  Google Scholar 

  17. Minden A, Karin M (1997) Regulation and function of the JNK subgroup of MAP kinases. Biochim Biophys Acta 1333:F85–F104

    Google Scholar 

  18. Keating MT, Escobedo JA, Williams LT (1988) Ligand activation causes a phosphorylation-dependent change in platelet-derived growth factor receptor conformation. J Biol Chem 263:12805–12808

    PubMed  CAS  Google Scholar 

  19. Uehara Y, Fukazawa H (1991) Use and selectivity of herbimycin A as inhibitor of protein-tyrosine kinases. Methods Enzymol 201:370–379

    Article  PubMed  CAS  Google Scholar 

  20. Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S-i, Itoh N, Shibuya M, Fukami Y (1987) Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 262:5592–5595

    PubMed  CAS  Google Scholar 

  21. Umezawa K, Hori T, Tajima H, Imoto M, Isshiki K, Takeuchi T (1990) Inhibition of epidermal growth factor-induced DNA synthesis by tyrosine kinase inhibitors. FEBS Lett 260:198–200

    Article  PubMed  CAS  Google Scholar 

  22. Gazit A, Yaish P, Gilon C, Levitzki A (1989) Tyrphostins I: synthesis and biological activity of protein tyrosine kinase inhibitors. J Med Chem 32:2344–2352

    Article  PubMed  CAS  Google Scholar 

  23. Fukazawa H, Mizuno S, Uehara Y (1990) Effects of herbimycin A and various SH-reagents on p60v-src kinase activity in vitro. Biochem Biophys Res Commun 173:276–282

    Article  PubMed  CAS  Google Scholar 

  24. Whitesell L, Mimnaugh EG, De CB, Myers CE, Neckers LM (1994) Inhibition of heat shock protein Hsp90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci USA 91:8324–8328

    Article  PubMed  CAS  Google Scholar 

  25. Imoto M, Kakeya H, Sawa T, Hayashi C, Hamada M, Takeuchi T, Umezawa K (1993) Dephostatin, a novel protein tyrosine phosphatase inhibitor produced by Streptomyces. I. Taxonomy, isolation, and characterization. J Antibiot (Tokyo) 46:1342–1346

    Article  CAS  Google Scholar 

  26. Hamaguchi T, Sudo T, Osada H (1995) RK-682, a potent inhibitor of tyrosine phosphatase, arrested the mammalian cell cycle progression at GI phase. FEBS Lett 372:54–58

    Article  PubMed  CAS  Google Scholar 

  27. Gescher A (1998) Analogs of staurosporine: potential anticancer drugs? Gen Pharmacol 31:721–728

    Article  PubMed  CAS  Google Scholar 

  28. Kawakami K, Futami H, Takahara J, Yamaguchi K (1996) UCN-01, 7-hydroxylstaurosporine, inhibits kinase activity of cyclin- dependent kinases and reduces the phosphorylation of the retinoblastoma susceptibility gene product in A549 human lung cancer cell line. Biochem Biophys Res Commun 219:778–783

    Article  PubMed  CAS  Google Scholar 

  29. Kobayashi E, Nakano H, Morimoto M, Tamaoki T (1989) Calphostin C (UCN-1028C), a novel microbial compound, is a highly potent and specific inhibitor of protein kinase C. Biochem Biophys Res Commun 159:548–553

    Article  PubMed  CAS  Google Scholar 

  30. Daniel LW, Civoli F, Rogers MA, Smitherman PK, Raju PA, Roederer M (1995) ET-18-OCH3 inhibits nuclear factor-κB activation by 12–0- tetradecanoylphorbol-13-acetate but not by tumor necrosis factor-alpha or interleukin 1α. Cancer Res 55:4844–4849

    PubMed  CAS  Google Scholar 

  31. Froscio M, Murray AW, Hurst NP (1989) Inhibition of protein kinase C activity by the antirheumatic drug auranofin. Biochem Pharmacol 38:2087–2089

    Article  PubMed  CAS  Google Scholar 

  32. Imoto M, Taniguchi Y, Umezawa K (1992) Inhibition of CDP-DG: inositol transferase by inostamycin. J Biochem (Tokyo) 112:299–302

    CAS  Google Scholar 

  33. Deguchi A, Imoto M, Umezawa K (1996) Inhibition of G1 cyclin expression in normal rat kidney cells by inostamycin, a phosphatidylinositol synthesis inhibitor. J Biochem (Tokyo) 120:1118–1122

    Article  CAS  Google Scholar 

  34. Kuo CJ, Chung J, Fiorentino DF, Flanagan WM, Blenis J, Crabtree GR (1992) Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase. Nature 358:70–73

    Article  PubMed  CAS  Google Scholar 

  35. Chung J, Kuo CJ, Crabtree GR, Blenis J (1992) Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinase. Cell 69:1227–1236

    Article  PubMed  CAS  Google Scholar 

  36. Kunz J, Henriquez R, Schneider U, Deuter-Reinhard M, Movva NR, Hall MN (1993) Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell 73:585–596

    Article  PubMed  CAS  Google Scholar 

  37. Brown EJ, Albers MW, Shin TB, Ichikawa K, Keith CT, Lane WS, Schreiber SL (1994) A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature 369:756–758

    Article  PubMed  CAS  Google Scholar 

  38. Brown EJ, Beal PA, Keith CT, Chen J, Shin TB, Schreiber SL (1995) Control of p70 s6 kinase by kinase activity of FRAP in vivo. Nature 377:441–446

    Article  PubMed  CAS  Google Scholar 

  39. Yano H, Nakanishi S, Kimura K, Hanai N, Saitoh Y, Fukui Y, Nonomura Y, Matsuda Y (1993) Inhibition of histamine secretion by wortmannin through the blockade of phosphatidylinositol 3-kinase in RBL-2H3 cells. J Biol Chem 268:25846–25856

    PubMed  CAS  Google Scholar 

  40. Muise-Helmericks RC, Grimes HL, Bellacosa A, Malstrom SE, Tsichlis PN, Rosen N (1998) Cyclin D expression is controlled post-transcriptionally via a phosphatidylinositol 3-kinase/Akt-dependent pathway. J Biol Chem 273:29864–29872

    Article  PubMed  CAS  Google Scholar 

  41. Hara M, Akasaka K, Akinaga S, Okabe M, Nakano H, Gomez R, Wood D, Uh M, Tamanoi F(1993) Identification of Ras farnesyltransferase inhibitors by microbial screening. Proc Natl Acad Sci USA 90:2281–2285

    Article  PubMed  CAS  Google Scholar 

  42. Kohl NE, Mosser SD, deSolms SJ, Giuliani EA, Pompliano DL, Graham SL, Smith RL, Scolnick EM, Oliff A, Gibbs JB (1993) Selective inhibition of ras-dependent transformation by a farnesyltransferase inhibitor. Science 260:1934–1937

    Article  PubMed  CAS  Google Scholar 

  43. James GL, Goldstein JL, Brown MS, Rawson TE, Somers TC, McDowell RS, Crowley CW, Lucas BK, Levinson AD, Marsters JJC (1993) Benzodiazepine peptidomimetics: potent inhibitors of Ras farnesylation in animal cells. Science 260:1937–1942

    Article  PubMed  CAS  Google Scholar 

  44. Keyomarsi K, Sandoval L, Band V, Pardee AB (1991) Synchronization of tumor and normal cells from GI to multiple cell cycles by lovastatin. Cancer Res 51:3602–3609

    PubMed  CAS  Google Scholar 

  45. DeClue JE, Vass WC, Papageorge AG, Lowy DR, Willumsen BM (1991) Inhibition of cell growth by lovastatin is independent of ras function. Cancer Res 51:712–717

    PubMed  CAS  Google Scholar 

  46. Vogt A, Qian Y, McGuire TF, Hamilton AD, Sebti SM (1996) Protein geranylgeranylation, not farnesylation, is required for the G1 to S phase transition in mouse fibroblasts. Oncogene 13:1991–1999

    PubMed  CAS  Google Scholar 

  47. Adnane J, Bizouarn FA, Qian Y, Hamilton AD, Sebti SM (1998) p21(WAF1/CIPI) is upregulated by the geranylgeranyltransferase I inhibitor GGTI-298 through a transforming growth factor beta- and Spl- responsive element: involvement of the small GTPase rhoA. Mol Cell Biol 18:6962–6970

    PubMed  CAS  Google Scholar 

  48. Kwon HJ, Yoshida M, Fukui Y, Horinouchi S, Beppu T (1992) Potent and specific inhibition of p60v-src protein kinase both in vivo and in vitro by radicicol. Cancer Res 52:6926–6930

    PubMed  CAS  Google Scholar 

  49. Ki SW, Kasahara K, Kwon HJ, Eishima J, Takesako K, Cooper JA, Yoshida M, Horinouchi S (1998) Identification of radicicol as an inhibitor of in vivo Ras/Raf interaction by the yeast two-hybrid screen system. J Antibiot 51:936–944

    Article  PubMed  CAS  Google Scholar 

  50. Roe SM, Prodromou C, O’Brien R, Ladbury JE, Piper PW, Pearl LH (1999) Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. J Med Chem 42:260–266

    Article  PubMed  CAS  Google Scholar 

  51. Alessi DR, Cuenda A, Cohen P, Dudley DT, Saltiel AR (1995) PD 098059 is a specific inhibitor of the activation of mitogen- activated protein kinase kinase in vitro and in vivo. J Biol Chem 270: 27489–94

    Article  PubMed  CAS  Google Scholar 

  52. Cuenda A, Rouse J, Doza YN, Meier R, Cohen P, Gallagher TF, Young PR, Lee JC (1995) SB203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1. FEBS Lett 364: 229–233

    Article  PubMed  CAS  Google Scholar 

  53. Fukuda M, Gotoh I, Adachi M, Gotoh Y, Nishida E (1997) A novel regulatory mechanism in the mitogen-activated protein (MAP) kinase cascade. Role of nuclear export signal of MAP kinase kinase. J Biol Chem 272: 32642–32648

    CAS  Google Scholar 

  54. Dingwall C, Laskey RA (1991) Nuclear targeting sequences: a consensus? Trends Biochem Sci 16: 478–481

    Article  PubMed  CAS  Google Scholar 

  55. Görlich D, Vogel F, Mills AD, Hartmann E, Laskey RA (1995) Distinct functions for the two importin subunits in nuclear protein import. Nature 377: 246–248

    Article  PubMed  Google Scholar 

  56. Siomi H, Dreyfuss G (1995) A nuclear localization domain in the hnRNP Al protein. J Cell Biol 129: 551–560

    Article  PubMed  CAS  Google Scholar 

  57. Bischoff FR, Ponstingl H(1991) Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCCl. Nature 354: 80–82

    Article  PubMed  CAS  Google Scholar 

  58. Bischoff FR, Krebber H, Kemph T, Hermes I, Ponstingl H (1995) Human RanGTPase activating protein RanGAP1 is a homolog of yeast RNAIp involved in messenger RNA processing and transport. Proc Natl Acad Sci USA 92: 1749–1753

    Article  PubMed  CAS  Google Scholar 

  59. Izaurralde E, Kutay U, von Kobbe C, Mattaj IW, Gorlick D (1997) The asymmetric distribution of the constituents of the Ran system is essential for transport into and out of the nucleus. EMBO J 16: 6535–6547

    Article  PubMed  CAS  Google Scholar 

  60. Fischer U, Huber J, Boelens WC, Mattaj IW, Lührmann R (1995) The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell 82: 475–483

    Article  PubMed  CAS  Google Scholar 

  61. Wen W, Meinkoth JL, Tsien RY, Taylor SS (1995) Identification of a signal of rapid export of proteins from the nucleus. Cell 82: 463–473

    Article  PubMed  CAS  Google Scholar 

  62. Adachi Y, Yanagida M (1989) Higher order chromosome structure is affected by coldsensitive mutations in a Schizosaccharomyces pombe gene crm1 + which encodes a 115-kD protein preferentially localized in the nucleus and at its periphery. J Cell Biol 108: 1159–1207

    Article  Google Scholar 

  63. Engel K, Kotlyarov A, Gaestel M (1998) Leptomycin B-sensitive nuclear export of MAPKAP kinase 2. EMBO J 17: 3363–3371

    Article  PubMed  CAS  Google Scholar 

  64. Wasylyk B, Hagman J, Gutierrez-Hartmann A (1998) Ets transcription factors: nuclear effectors of the Ras-MAP-kinase signaling pathway. Trends Biochem Sci 23: 213–216

    Article  PubMed  CAS  Google Scholar 

  65. Karin M, Liu Zg, Zandi E (1997) AP-1 function and regulation. Curr Opin Cell Biol 9: 240–246

    Article  PubMed  CAS  Google Scholar 

  66. Montminy M (1997) Transcriptional regulation by cyclic AMP. Annu Rev Biochem 66: 807–822

    Article  PubMed  CAS  Google Scholar 

  67. Turner BM (1991) Histone acetylation and control of gene expression. J Cell Sci 99: 13–20

    PubMed  CAS  Google Scholar 

  68. Taunton J, Hassig CA, Schreiber SL (1996) A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 272: 408–411

    Article  PubMed  CAS  Google Scholar 

  69. Kijima M, Yoshida M, Sugita K, Horinouchi S, Beppu T (1993) Trapoxin, an antitumor cyclic tetrapeptide, is an irreversible inhibitor of mammalian histone deacetylase. J Biol Chem 268: 22429–22435

    PubMed  CAS  Google Scholar 

  70. Wade PA, Pruss D, Wolfe AP (1997) Histone acetylation: chromatin in action. Trends Biochem Sci 22: 128–132

    Article  PubMed  CAS  Google Scholar 

  71. Torchia J, Glass C, Rosenfeld MG (1998) Co-activators and co-repressors in the integration of transcriptional responses. Curr Opin Cell Biol 10: 373–383

    Article  PubMed  CAS  Google Scholar 

  72. Janknecht R, Hunter T (1996) A growing coactivator network. Nature 383: 22–23

    Article  PubMed  CAS  Google Scholar 

  73. Yang Xi, Ogryzko VV, Nishikawa J, Howard BH, Nakatani Y (1996) A p300/CBP-associated factor that competes with the adenoviral oncoprotein EIA. Nature 382: 319–324

    Article  PubMed  CAS  Google Scholar 

  74. Petrij F, Giles RH, Dauwerse HG, Saris JJ, Hennekam RCM, Masuno M, Tommerup N, van Ommen G-JB, Goodman RH, Peters DJM, Breuning MH (1995) Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 376: 348–351

    Article  PubMed  CAS  Google Scholar 

  75. Gu W, Roeder RG (1997) Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 90: 595–606

    Article  PubMed  CAS  Google Scholar 

  76. Boyes J, Byfield P, Nakatani Y, Ogryzko V (1998) Regulation of activity of the transcription factor GATA-1 by acetylation. Nature 396: 594–598

    Article  PubMed  CAS  Google Scholar 

  77. Nishi K, Yoshida M, Fujiwara D, Nishikawa M, Horinouchi S, Beppu T (1994) Leptomycin B targets a regulatory cascade of crml, a fission yeast nuclear protein, involved in control of higher order chromosome structure and gene expression. J Biol Chem 269: 6320–6324

    PubMed  CAS  Google Scholar 

  78. Wolff B, Sanglier J-J, Wang Y (1997) Leptomycin B is an inhibitor of nuclear export: inhibition of nucleo-cytoplasmic translocation of the human immunodeficiency virus type 1 (HIV-1) Rev protein and Rev-dependent mRNA. Chem Biol 4: 139–147

    Article  PubMed  CAS  Google Scholar 

  79. Fornerod M, Deursen Jv, Baal Sv, Reynolds A, Davis D, Murti KG, Fransen J, Grosveld G (1997) The human homologue of yeast CRM 1 is in a dynamic subcomplex with CAN/ Nup214 and a novel nuclear pore component Nup 88. EMBO J 16: 807–816

    Article  PubMed  CAS  Google Scholar 

  80. Kudo N, Khochbin S, Nishi K, Kitano K, Yanagida M, Yoshida M, Horinouchi S (1997) Molecular cloning and cell cycle-dependent expression of mammalian CRM 1, a protein involved in nuclear export of proteins. J Biol Chem 272: 29742–29751

    Article  PubMed  CAS  Google Scholar 

  81. Fornerod M, Ohno M, Yoshida M, Mattaj IW (1997) CRMI is an export receptor for leucine-rich nuclear export signals. Cell 90: 1051–1060

    Article  PubMed  CAS  Google Scholar 

  82. Stade K, Ford CS, Guthrie C, Weis K (1997) Exportin 1 (Crmlp) is an essential nuclear export factor. Cell 90: 1041–1050

    Article  PubMed  CAS  Google Scholar 

  83. Fukuda M, Asano S, Nakamura T, Adachi M, Yoshida M, Yanagida M, Nishida E (1997) CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature 390: 308–311

    Article  PubMed  CAS  Google Scholar 

  84. Kudo N, Wolff B, Sekimoto T, Schreiner EP, Yoneda Y, Yanagida M, Horinouchi S, Yoshida M (1998) Leptomycin B inhibition of signal-mediated nuclear export by direct binding to CRM 1. Exp Cell Res 242: 540–547

    Article  PubMed  CAS  Google Scholar 

  85. Kudo N, Matsumori N, Taoka H, Fujiwara D, Schreiner EP, Wolff B, Yoshida M, Horinouchi S (1999) Leptomycin B inactivates CRMI/exportin 1 by covalent modification at a cysteine residue in the central conserved region. Proc Natl Acad Sci USA 96: 9112–9117

    Article  PubMed  CAS  Google Scholar 

  86. Goto M, Masegi M, Yamauchi T, Chiba K, Kuboi Y, Harada K, Naruse N (1998) K1115 A, a new anthraquinone derivative that inhibits the binding of activator protein-1 (AP-1) to its recognition sites. I. Biological activities. J Antibiot 51: 539–544

    Article  PubMed  CAS  Google Scholar 

  87. Sakai Y, Yoshida T, Tsujita T, Ochiai K, Agatsuma T, Saitoh Y, Tanaka F, Akiyama T, Akinaga S, Mizukami T (1997) GE3, a novel hexadepsipeptide antitumor antibiotic, produced by Streptomyces sp. I. Taxonomy, production, isolation, physico-chemical properties, and biological activities. J Antibiot 50: 659–664

    Article  PubMed  CAS  Google Scholar 

  88. Yoshida M, Horinouchi S, Beppu T (1995) Trichostatin A and trapoxin: novel chemical probes for the role of histone acetylation in chromatin structure and function. Bio Essays 17: 423–430

    CAS  Google Scholar 

  89. Yoshida M, Kijima M, Akita M, Beppu T (1990) Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem 265: 17174–17179

    PubMed  CAS  Google Scholar 

  90. Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, Bird A (1998) Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393: 386–389

    Article  PubMed  CAS  Google Scholar 

  91. Nakajima H, Kim YB, Terano H, Yoshida M, Horinouchi S (1998) FR901228, a potent antitumor antibiotic, is a novel histone deacetylase inhibitor. Exp Cell Res 241: 126–133

    Article  PubMed  CAS  Google Scholar 

  92. Kwon HJ, Owa T, Hassig CA, Shimada J, Schreiber SL (1998) Depudecin induces morphological reversion of transformed fibroblasts via the inhibition of histone deacetylase. Proc Natl Acad Sci USA 95: 3356–3361

    Article  PubMed  CAS  Google Scholar 

  93. Kim YB, Lee K-H, Sugita K, Yoshida M, Horinouchi S (1999) Oxamflatin is a novel antitumor compound that inhibits mammalian histone deacetylase. Oncogene 18: 2461–2470

    Article  PubMed  CAS  Google Scholar 

  94. Pardee AB (1989) GI events and regulation of cell proliferation. Science 246: 603–608

    Article  PubMed  CAS  Google Scholar 

  95. Norbury C, Nurse P (1992) Animal cell cycles and their control. Annu Rev Biochem 61: 441–470

    Article  PubMed  CAS  Google Scholar 

  96. Lee MG, Nurse P (1987) Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature 327: 31–35

    Article  PubMed  CAS  Google Scholar 

  97. Morgan DO (1995) Principles of CDK regulation. Nature 374: 131–134

    Article  PubMed  CAS  Google Scholar 

  98. Lukas J, Bartkova J, Rohde M, Strauss M, Bartek J (1995) Cyclin D1 is dispensable for G1 control in retinoblastoma gene-deficient cells independently of cdk4 activity. Mol Cell Biol 15: 2600–2611

    PubMed  CAS  Google Scholar 

  99. Sherr CJ (1993) Mammalian G1 cyclins. Cell 73: 1059–1065

    Article  PubMed  CAS  Google Scholar 

  100. Hilt W, Wolf DH (1996) Proteasomes: destruction as a programme. Trends Biochem Sci 21: 96–102

    PubMed  CAS  Google Scholar 

  101. Solomon MJ (1993) Activation of the various cyclin/cdc2 protein kinases. Curr Opin Cell Biol 5:180–186

    Article  PubMed  CAS  Google Scholar 

  102. Nurse P (1990) Universal control mechanism regulating onset of M-phase. Nature 344:503–508

    Article  PubMed  CAS  Google Scholar 

  103. Nigg EA (1995) Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle. Bioessays 17:471–480

    Article  PubMed  CAS  Google Scholar 

  104. Yaffe MB, Schutkowski M, Shen M, Zhou XZ, Stukenberg PT, Rahfeld JU, Xu J, Kuang J, Kirschner MW, Fischer G, Cantley LC, Lu KP (1997) Sequence-specific and phosphorylation-dependent proline isomerization: a potential mitotic regulatory mechanism. Science 278:1957–1960

    Article  PubMed  CAS  Google Scholar 

  105. Shen M, Stukenberg PT, Kirschner MW, Lu KP (1998) The essential mitotic peptidylprolyl isomerase Pinl binds and regulates mitosis-specific phosphoproteins. Genes Dev 12:706–720

    Article  PubMed  CAS  Google Scholar 

  106. Hennig L, Christner C, Kipping M, Schelbert B, Rucknagel KP, Grabley S, Kullertz G, Fischer G (1998) Selective inactivation of parvulin-like peptidyl-prolyl cis/trans isomerases by juglone. Biochemistry 37:5953–5960

    Article  PubMed  CAS  Google Scholar 

  107. Hagting A, Karlsson C, Clute P, Jackman M, Pines J (1998) MPF localization is controlled by nuclear export. EMBO J 17:4127–4138

    Article  PubMed  CAS  Google Scholar 

  108. Hunter T, Pines J (1994) Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell 79:573–582

    Article  PubMed  CAS  Google Scholar 

  109. Elledge SJ, Harper JW (1994) Cdk inhibitors: on the threshold of checkpoints and development. Curr Opin Cell Biol 6:847–852

    Article  PubMed  CAS  Google Scholar 

  110. Grana X, Reddy EP (1995) Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 11:211–219

    PubMed  CAS  Google Scholar 

  111. Kawada M, Yamagoe S, Murakami Y, Suzuki K, Mizuno S, Uehara Y (1997) Induction of p27Kipl degradation and anchorage independence by Ras through the MAP kinase signaling pathway. Oncogene 15:629–637

    Article  PubMed  CAS  Google Scholar 

  112. Serrano M, Hannon GJ, Beach D (1993) A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366:704–707

    Article  PubMed  CAS  Google Scholar 

  113. Lukas J, Parry D, Aagaard L, Mann DJ, Bartkova J, Strauss M, Peters G, Bartek J (1995) Retinoblastoma-protein-dependent cell-cycle inhibition by the tumour suppressor p16. Nature 375:503–506

    Article  PubMed  CAS  Google Scholar 

  114. Kamijo T, Zindy F, Roussel MF, Quelle DE, Downing JR, Ashmun RA, Grosveld G, Sherr CJ (1997) Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell 91:649–659

    Article  PubMed  CAS  Google Scholar 

  115. Bates S, Phillips AC, Clark PA, Stott F, Peters G, Ludwig RL, Vousden KH (1998) p14ARF links the tumour suppressors RB and p53. Nature 395:124–125

    Article  PubMed  CAS  Google Scholar 

  116. Zhang Y, Xiong Y, Yarbrough WG (1998) ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell 92:725–734

    Article  PubMed  CAS  Google Scholar 

  117. Bartek J, Bartkova J, Lukas J (1996) The retinoblastoma protein pathway and the restriction point. Curr Opin Cell Biol 8:805–814

    Article  PubMed  CAS  Google Scholar 

  118. Brehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ, Kouzarides T (1998) Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature 391:597–601

    Article  PubMed  CAS  Google Scholar 

  119. Magnaghi JL, Groisman R, Naguibneva I, Robin P, Lorain S, Le VJ, Troalen F, Trouche D, Harel BA (1998) Retinoblastoma protein represses transcription by recruiting a histone deacetylase. Nature 391:601–605

    Article  CAS  Google Scholar 

  120. Kitagawa M, Okabe T, Ogino H, Matsumoto H, Suzuki-Takahashi I, Kokubo T, Higashi H, Saitoh S, Taya Y, Yasuda H, Ohba Y, Nishimura S, Tanaka N, Okuyama A (1993) Butyrolactone I, a selective inhibitor of cdk2 and cdc2 kinase. Oncogene 8:2425–2432

    PubMed  CAS  Google Scholar 

  121. Abe K, Yoshida M, Usui T, Horinouchi S, Beppu T (1991) Highly synchronous culture of fibroblasts from G2 block caused by staurosporine, a potent inhibitor of protein kinases. Exp Cell Res 192:122–127

    Article  PubMed  CAS  Google Scholar 

  122. Schnier JB, Nishi K, Goodrich DW, Bradbury EM (1996) G1 arrest and down-regulation of cyclin E/cyclin-dependent kinase 2 by the protein kinase inhibitor staurosporine are dependent on the retinoblastoma protein in the bladder carcinoma cell line 5637. Proc Natl Acad Sci USA 93:5941–5946

    Article  PubMed  CAS  Google Scholar 

  123. Meijer L, Borgne A, Mulner 0, Chong JP, Blow JJ, Inagaki N, Inagaki M, Delcros JG, Moulinoux JP (1997) Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur J Biochem 243:527–536

    Article  PubMed  CAS  Google Scholar 

  124. Kakeya H, Onose R, Liu PC, Onozawa C, Matsumura F, Osada H (1998) Inhibition of cyclin D1 expression and phosphorylation of retinoblastoma protein by phosmidosine, a nucleotide antibiotic. Cancer Res 58:704–710

    PubMed  CAS  Google Scholar 

  125. Takuwa N, Fukui Y, Takuwa Y (1999) Cyclin D1 expression mediated by phosphatidylinositol 3-kinase through mTOR-p70(S6K)-independent signaling in growth factor-stimulated NIH 3T3 fibroblasts. Mol Cell Biol 19:1346–1358

    PubMed  CAS  Google Scholar 

  126. Gorospe M, Liu Y, Xu Q, Chrest FJ, Holbrook NJ (1996) Inhibition of G1 cyclindependent kinase activity during growth arrest of human breast carcinoma cells by prostaglandin A2. Mol Cell Biol 16:762–770

    PubMed  CAS  Google Scholar 

  127. Fenteany G, Standaert RF, Lane WS, Choi S, Corey EJ, Schreiber SL(1995) Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. Science 268:726–731

    Article  PubMed  CAS  Google Scholar 

  128. Lane DP (1992) Cancer. p53, guardian of the genome. Nature 358:15–16.

    Article  PubMed  CAS  Google Scholar 

  129. Shieh SY, Ikeda M, Taya Y, Prives C (1997) DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 91:325–334

    Article  PubMed  CAS  Google Scholar 

  130. Banin S, Moyal L, Shieh S, Taya Y, Anderson CW, Chessa L, Smorodinsky NI, Prives C, Reiss Y, Shiloh Y, Ziv Y (1998) Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 281:1674–1677

    Article  PubMed  CAS  Google Scholar 

  131. Stommel JM, Marchenko ND, Jimenez GS, Moll UM, Hope TJ, Wahl GM (1999) A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of subcellular localization and p53 activity by NES masking. EMBO J 18:1660–1672

    Article  PubMed  CAS  Google Scholar 

  132. Lopez-Girona A, Furnari B, Mondesert 0, Russell P (1999) Nuclear localization of Cdc25 is regulated by DNA damage and a 14–3-3 protein. Nature 397:172–175

    Article  PubMed  CAS  Google Scholar 

  133. Yang J, Winkler K, Yoshida M, Kornbluth S (1999) Maintenance of G2 arrest in the Xenopus oocyte: A role for 14–3-3-mediated inhibition of Cdc25 nuclear import. EMBO J 18:2174–2183

    Article  PubMed  CAS  Google Scholar 

  134. Kumagai A, Guo Z, Emami KH, Wang SX, Dunphy WG (1998) The Xenopus Chkl protein kinase mediates a caffeine-sensitive pathway of checkpoint control in cell-free extracts. J Cell Biol 142:1559–1569

    Article  PubMed  CAS  Google Scholar 

  135. Schlegel R, Pardee AB (1986) Caffeine-induced uncoupling of mitosis from the completion of DNA replication in mammalian cells. Science 232:1264–1266

    Article  PubMed  CAS  Google Scholar 

  136. Andreassen PR, Margolis RL (1992) 2-Aminopurine overrides multiple cell cycle checkpoints in BHK cells. Proc Nati Acad Sci USA 89:2272–2726

    Article  CAS  Google Scholar 

  137. Yoshida M, Usui T, Tsujimura K, Inagaki M, Beppu T, Horinouchi S (1997) Biochemical differences between staurosporine-induced apoptosis and premature mitosis. Exp Cell Res 232:225–239

    Article  PubMed  CAS  Google Scholar 

  138. Shao RG, Cao CX, Shimizu T, O’Connor PM, Kohn KW, Pommier Y (1997) Abrogation of an S-phase checkpoint and potentiation of camptothecin cytotoxicity by 7-hydroxystaurosporine (UCN-01) in human cancer cell lines, possibly influenced by p53 function. Cancer Res 57:4029–4035

    PubMed  CAS  Google Scholar 

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Authors
  1. Minoru Yoshida
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Editors and Affiliations

  1. Antibiotics Laboratory, RIKEN, Hirosawa 2-1, 351-0198, Wako, Saitama, Japan

    Hiroyuki Osada (Professor) (Professor)

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© 2000 Springer-Verlag Tokyo

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Yoshida, M. (2000). Cell Proliferation: From Signal Transduction to Cell Cycle. In: Osada, H. (eds) Bioprobes. Springer, Tokyo. https://doi.org/10.1007/978-4-431-65927-3_2

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  • DOI: https://doi.org/10.1007/978-4-431-65927-3_2

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