Skip to main content
SpringerLink
Log in

Inhibitors of the Cip/Kip Family

  • Chapter
Book cover Cyclin Dependent Kinase (CDK) Inhibitors

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 227))

Abstract

Although cyclin-dependent kinase inhibitors of the Cip/Kip family were the first to be discovered in mammalian cells, and they are the best characterized to date, fundamental mysteries remain concerning their biological roles and their regulation. The family, consisting so far of three members, is characterized by a C-terminal Cdk-inhibitory domain with a shared core homology and unrelated C-terminal domains of varying size (Lee et al. 1995; Matsuoka et al. 1995). To date, a function has been ascribed to the C-terminal domain of only one member of the family. The C terminus of the p21 has been shown to be able to bind and inactivate the function of the DNA polymerase-δ processivity factor, PCNA (J. Chen et al. 1995, 1996a, b; Goubin and Ducommun 1995; Luo et al. 1995; Nakanishi et al. 1995b; Warbrick et al. 1995; Waga et al. 1994).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Agrawal D, Hauser P, McPherson F, Dong F, Garcia A, Pledger WJ (1996) Repression of p27kip1 synthesis by platelet-derived growth factor in BALB/c 3T3 cells. Mol Cell Biol 16: 4327–4336

    PubMed  CAS  Google Scholar 

  • Aprelikova O. Xiong Y, Liu ET (1995) Both p 1 and p21 families of cyclin-dependent kinase ( CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by the CDK-activating kinase. J Biol Chem 270: 18195–18197

    Google Scholar 

  • Artuso M, Esteve A, Bresil H, Vuillaume M, Hall J (1995) The role of the Ataxia telangiectasia gene in the p53, WAFI/CIPI(p21)- and GADD45-mediated response to DNA damage produced by ionising radiation. Oncogene I1: 1427–1435

    Google Scholar 

  • Bae I, Fan S, Bhatia K, Kohn KW, Fornace AJ, O’Connor PM (1995) Relationships between GI arrest and stability of the p53 and p2lCipl/Wafl proteins following gamma-irradiation of human lymphoma cells. Cancer Res 55: 2387–2393

    PubMed  CAS  Google Scholar 

  • Barboule N, Mazars P, Baldin V, Vidal S, Jozan S, Martel P, Valette A (1995) Expression of p2I WAFT/ CIPI is heterogeneous and unrelated to proliferation index in human ovarian carcinoma. Intl Cancer 63: 611–615

    Article  CAS  Google Scholar 

  • Bates S, Vousden KH (1996) p53 in signalling checkpoint arrest or apoptosis. Curr Opin Genet Dev 6: 12–18

    Google Scholar 

  • Bhatia K, Fan S, Spangler G, Weintraub M, O’Connor PM, Judde JG, Magrath I (1995) A mutant p21 cyclin-dependent kinase inhibitor isolated from a Burkitt’s lymphoma. Cancer Res 55: 1431–1435

    PubMed  CAS  Google Scholar 

  • Brugarolas J, Chandrasekaran C, Gordon JI, Beach D, Jacks T, Hannon G.1 (1995) Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature 377: 552–557

    CAS  Google Scholar 

  • Bullrich F, MacLachlan TK, Sang N, Druck T, Veronese ME, Allen SL, Chiorazzi N, Koff A, Heubner K, Croce CM, et al. (1995) Chromosomal mapping of members of the cdc2 family of protein kinases, cdk3, cdk6, PISSLRE, and PITALRE, and a cdk inhibitor, p27Kipl, to regions involved in human cancer. Cancer Res 55: 1199–1205

    PubMed  CAS  Google Scholar 

  • Chen IT, Akamatsu M, Smith ML, Lung FD, Duba D, Roller PP, Fornace AJ, O’Connor PM (1996a) Characterization of p2lCipl/Wafl peptide domains required for cyclin E/Cdk2 and PCNA interaction. Oncogene 12: 595–607

    PubMed  CAS  Google Scholar 

  • Chen J, Jackson PK, Kirschner MW, Dutta A (1995) Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA. Nature 374: 386–388

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Peters R, Saha P, Lee P, Theodoras A, Pagano M, Wagner G, Dutta A (1996b) A 39 amino acid fragment of the cell cycle regulator p2I is sufficient to bind PCNA and partially inhibit DNA replication in vivo. Nucleic Acids Res 24: 1727–1733

    Article  PubMed  CAS  Google Scholar 

  • ChenJ, Saha P, Kornbluth S, Dynlacht B, Dutta A (1996e) Cyclin-binding motifs are essential for the function of p21kip1. Mol Cell Biol 19: 4673–4682

    Google Scholar 

  • Chen J, Willingham T, Shuford M, Nisen PD (1996d) Tumor suppression and inhibition of aneuploid cell accumulation in human brain tumor cells by ectopic overexpression of the cyclin-dependent kinase inhibitor p27KIP1. J Clin Invest 97: 1983–1988

    Article  PubMed  CAS  Google Scholar 

  • Coats S, Flanagan WM, Nourse J, Roberts JM (1996) Requirement of p27kip1 for restriction point control of the fibroblast cell cycle. Science 272: 877–880

    Article  PubMed  CAS  Google Scholar 

  • Deng C, Zhang P, Harper JW, Elledge SJ, Leder P (1995) Mice lacking p21CIPI/WAFT undergo normal development, but are defective in GI checkpoint control. Cell 82: 675–684

    Article  PubMed  CAS  Google Scholar 

  • Dulic V, Kaufmann WK, Wilson Si, Tlsty TD, Lees E, Harper JW, Elledge SJ, Reed SI (1994) p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced GI arrest. Cell 76: 1013–1023

    Google Scholar 

  • EI-Deiry W, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B (1993) WAFT, a potential mediator of p53 tumor suppression. Cell 75: 817–825

    Article  Google Scholar 

  • EI-Deiry W, Harper JW, O’Connor PM, Velculescu VE, Canman CE, Jackman J, Pietenpol JA, Burrell M, Hill DE, Wang Y, et al. (1994) WAFI/CIPI is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 54: 1169–1174

    Google Scholar 

  • Ezhevsky SA, Toyoshima H, Hunter T, Scott DW (1996) Role of cyclin A and p27 in anti-IgM-induced GI growth arrest of murine B-cell lymphomas. Mol Biol Cell 7: 553–564

    PubMed  CAS  Google Scholar 

  • Fang F, Orend G, Watanabe N, Hunter T, Ruoslahti E (1996) Dependence of cyclin E-CDK2 kinase activity on cell anchorage. Science 271: 499–502

    Article  PubMed  CAS  Google Scholar 

  • Fero ML, Rivkin M, Tasch M, Porter P. Carow CE, Firpo E, Polyak K, Tsai LH, Broudy V, Perlmutter RM, Kaushansky K, Roberts JM (1996) A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kipl)-deficient mice. Cell 85: 733–744

    Article  PubMed  CAS  Google Scholar 

  • Ferrando AA, Balbin M, Pendas AM, Vizoso F, Velasco G, Lopez-Otin C (1995) Mutational analysis of the human cyclin-dependent kinase inhibitor p27K’rj in primary breast carcinomas. Hum Genet 967: 91–94

    Google Scholar 

  • Fotedar R, Fitzgerald P, Rousselle T, Cannella D, Doree M. Messier H, Fotedar A (1996) p2I contains independent binding sites for cyclin and cdk2:both sites are required to inhibit cdk2 kinase activity. Oncogene 12: 2155–2164

    Google Scholar 

  • Gao X, Chen YQ, Wu N. Grignon DJ, Sakr W, Porter AT, Honn KV (1995) Somatic mutations of the WAFI/CIPI gene in primary prostate cancer. Oncogene 11: 1395–1398

    PubMed  CAS  Google Scholar 

  • Goubin F, Ducommun B (1995) Identification of binding domains on the p2lCipl cyclin-dependent kinase inhibitor. Oncogene 10: 2281–2287

    PubMed  CAS  Google Scholar 

  • Gu Y, Turck CW, Morgan DO (1993) Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit. Nature 366: 707–710

    Article  PubMed  CAS  Google Scholar 

  • Gulbis JM, Kelman Z, Hurwitz J, O’Donnel M, Kuriyan, J (1996) Structure of the C-terminal region of p2lwar /Ci~~ complexed with human PCNA. Cell 87: 297–306

    Article  PubMed  CAS  Google Scholar 

  • Guo K, Wang J, Andres V, Smith RC, Walsh K (1995) MyoD-induced expression of p21 inhibits cyclin- dependent kinase activity upon myocyte terminal differentiation. Mol Cell Biol 15: 3823–3829

    PubMed  CAS  Google Scholar 

  • Halevy O, Novitch BG, Spicer DB, Skapek SX, Rhee J, Hannon GJ, Beach D, Lassar AB (1995) Correlation of terminal cell cycle arrest of skeletal muscle with induction of p21 by MyoD. Science 267: 1018–1021

    Article  PubMed  CAS  Google Scholar 

  • Hall M, Bates S, Peters G (1995) Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to cyclins. Oncogene 11: 1581–1588

    PubMed  CAS  Google Scholar 

  • Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge S J (1993) The p21 Cdk-interacting protein Cipl is a potent inhibitor of GI cyclin-dependent kinases. Cell 75: 805–816

    Article  PubMed  CAS  Google Scholar 

  • Harper JW, Elledge SJ, Keyomarsi K et al. (1995) Inhibition of cyclin-dependent kinases by p21. Mol Biol Cell 6: 387–400

    PubMed  CAS  Google Scholar 

  • Hatada I, Mukai T (1995) Genomic imprinting of p57KIP2, a cyclin-dependent kinase inhibitor, in mouse. Nat Genet 11: 204–206

    Article  PubMed  CAS  Google Scholar 

  • Hengst L, Reed SI (1996) Translational control of p27Kipl accumulation during the cell cycle. Science 271: 1861–1864

    Article  PubMed  CAS  Google Scholar 

  • Hengst L, Dulic V, Slingerland JM, Lees E, Reed SI (1994) A cell cycle-regulated inhibitor of cyclindependent kinases. Proc. Natl Acad Sci USA 91: 5291–5295

    Google Scholar 

  • Hirama T, Koefer HP (1996) Role of cyclin-dependent kinase inhibitors in the development of cancer. Blood 86: 841–854

    Google Scholar 

  • Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253: 49–53

    Google Scholar 

  • Kastan MB, Zhan Q, EI-Deiry WS, Carrier F, Jacks T, Walsh WV, Plunkett BS, Vogelstein B, Fornace AJ (1992) A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia telangiectasia. Cell 71: 587–597

    Article  PubMed  CAS  Google Scholar 

  • Kato JY, Matsuoka M, Polyak K. Massague J, Sherr CJ (1994) Cyclic AMP-induced GI phase arrest mediated by an inhibitor (p27Kipl) of cyclin-dependent kinase 4 activation. Cell 79: 487–496

    Article  PubMed  CAS  Google Scholar 

  • Kawamata N, Morosetti R, Miller CW, Park D, Spirin KS, Nakamaki T, Takeuchi S, Hatta Y, Simpson J, Wilcyznski S, et al. (1995) Molecular analysis of the cyclin-dependent kinase inhibitor gene p27/ Kip1 in human malignancies. Cancer Res 55: 2266–2269

    PubMed  CAS  Google Scholar 

  • Kawamata N, Seriu T, Koeffler HP, Bartram CR (1996) Molecular analysis of the cyclin-dependent kinase inhibitor family: p16(CDKN2/MTSI/INK4A), p18(INK4C) and p27(Kipl) genes in neuroblastomas. Cancer 77: 570–575

    Article  PubMed  CAS  Google Scholar 

  • Kiwacki RW, Hengst L, Tennant L, Reed SI, Wright PE (1996) Structural studies of p21 Wafl/Cipl/Sdil in the free and Cdk2 bound state: conformational disorder mediates binding diversity. Proc Natl Acad Sci USA 93: 11504–11507

    Article  Google Scholar 

  • Kiyokawa H, Kineman RD, Manova TK, Soares VC, Hoffman ES, Ono M, Khanam D, Hayday AC, Frohman LA, Koff A (1996) Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27(Kip1). Cell 85: 721–732

    Article  PubMed  CAS  Google Scholar 

  • Kondo M, Matsuoka S. Uchida K, Osada H, Nagatake M, Takagi K, Harper JW, Takahashi T, Elledge SJ, Takahashi T (1996) Selective maternal-allele loss in human lung cancers of the maternally expressed p57KIP2 gene at 11p15.5. Oncogene 12: 1365–1368

    CAS  Google Scholar 

  • Kranenburg O, Scharnhorst V, Van der Eb A, Zantema A (1995) Inhibition of cyclin-dependent kinase activity triggers neuronal differentiation of mouse neuroblastoma cells. J Cell Biol 131: 227–234

    Article  PubMed  CAS  Google Scholar 

  • Lee MH, Reynisdottir I, Massague J (1995) Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Genes Dev 9: 639–649

    Article  PubMed  CAS  Google Scholar 

  • Lee MH, Nikolic M, Baptista CA, Lai E, Tsai LH, Massague J (1996) The brain-specific activator p35 allows CdkS to escape inhibition by p27Kip1 in neurons. Proc Natl Acad Sci USA 93: 3259–3263

    Article  PubMed  CAS  Google Scholar 

  • Levine AJ, Momand J, Finlay CA (1991) The p53 tumor suppressor gene. Nature 351: 453–456

    Article  PubMed  CAS  Google Scholar 

  • Li R, Waga S, Hannon GJ, Beach D. Stillman B (1994) Differential effects by the p21 CDK inhibitor on PCNA-dependent DNA replication and repair. Nature 371: 534–537

    Article  PubMed  CAS  Google Scholar 

  • Li R, Hannon GJ, Beach D, Stillman B (1996) Subcellular distribution of p21 and PCNA in normal and repair-deficient cells following DNA damage. Curr Biol 6: 189–199

    Article  PubMed  CAS  Google Scholar 

  • Liu M, Felling JC (1995) UV-B/A irradiation of mouse keratinocytes results in p53-mediated WAFT/ CIP I expression. Oncogene 10: 1955–1960

    PubMed  CAS  Google Scholar 

  • Liu M, Lee MH, Cohen M, Bommakanti M, Freedman LP (1996) Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev 10: 142–153

    Article  PubMed  CAS  Google Scholar 

  • Luo Y, Hurwitz J, Massague J (1995) Cell-cycle inhibition by independent CDK and PCNA binding domains in p2lCipl. Nature 375: 159–161

    Article  PubMed  CAS  Google Scholar 

  • Macleod KF, Sherry N, Hannon G, Beach D, Tokino T, Kinzler K, Vogelstein B, Jacks T (1995) p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. Genes Dev 9: 935–944

    Google Scholar 

  • Mal A, Poon R, Howe PH, Toyoshima H, Hunter T, Harter ML (1996) Inactivation of p27K’Pl by the viral EIA oncoprotein in TGF-(3 treated cells. Nature 380: 262–265

    Article  PubMed  CAS  Google Scholar 

  • Matsuoka S, Edwards MC, Bai C, Parker S, Zhang P, Baldini A, Harper JW, Elledge SJ (1995) p57KIP2, a structurally distinct member of the p21CIPl Cdk inhibitor family, is a candidate tumor suppressor gene. Genes Dev 9: 650–662

    Google Scholar 

  • Matsuoka S, Thompson JS, Edwards MC, Barletta JM, Grundy P, Kalikin LM, Harper JW, Elledge Si, Feinberg AP (1996) Imprinting of the gene encoding a human cyclin-dependent kinase inhibitor, p57kip2, on chromosome 11p15. Proc Natl Acad Sci USA 93: 3026–3030

    Article  PubMed  CAS  Google Scholar 

  • McDonald ER, Wu GS, Waldman T, El Deiry WS (1996) Repair defect in p21 WAFI/CIPI-/- human cancer cells. Cancer Res 56: 2250–2255

    PubMed  CAS  Google Scholar 

  • Medrano EE, Im S, Yang F, Abdel MZ (1995) Ultraviolet B light induces GI arrest in human melanocytes by prolonged inhibition of retinoblastoma protein phosphorylation associated with long-term expression of the p21Waf-1/SDI-I/Cip-1 protein. Cancer Res 55: 4047–4052

    PubMed  CAS  Google Scholar 

  • Nakanishi M, Robetorye RS, Adami GR, Pereira SO, Smith JR (1995a) Identification of the active region of the DNA synthesis inhibitory gene p2lSdil/CIPI/WAFI. Embo J 14: 555–563

    PubMed  CAS  Google Scholar 

  • Nakanishi M, Robetorye RS, Pereira SO, Smith JR (1995b) The C-terminal region of p21SD11/WAF1/ CIPI is involved in proliferating cell nuclear antigen binding but does not appear to be required for growth inhibition. J Biol Chem 270: 17060–17063

    Article  PubMed  CAS  Google Scholar 

  • Nakayama K, Ishida N, Shirane M, Inomata A, Inoue T, Shishido N, Horii I, Loh DY, Nakayama K (1996) Mice lacking p27(Kipl) display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors. Cell 85: 707–720

    Article  PubMed  CAS  Google Scholar 

  • Noda A, Ning Y, Venable SF, Pereira SO, Smith.JR (1994) Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp Cell Res 211: 90–98

    Article  PubMed  CAS  Google Scholar 

  • Nourse J, Firpo E, Flanagan WM, Coats S, Polyak K, Lee MH, Massague J, Crabtree GR, Roberts JM (1994) Interleukin-2-mediated elimination of the p27Kipl cyclin-dependent kinase inhibitor prevented by rapamycin. Nature 372: 570–573

    Article  PubMed  CAS  Google Scholar 

  • Orlow I, Iavarone A, Crider-Miller SJ, Bonilla F, Latres E, Lee M-H, Gerald WL, Massague J, Weissman BE, Cordon-Cardo C (1996) Cyclin-dependent kinase inhibitor, p57Kip2 in soft tissue sarcomas and Wilm’s tumors. Cancer Res 56: 1219–1221

    PubMed  CAS  Google Scholar 

  • Pagano M, Tam SW, Theodoras AM, Beer-Romero P, Del Sal G, Chau V, Yew PR, Draetta GF, Rolfe M (1995) Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science 269: 682–685

    Article  PubMed  CAS  Google Scholar 

  • Pan ZQ, Reardon JT, Li L, Flores RH, Legerski R, Sancar A, Hurwitz J (1995) Inhibition of nucleotide excision repair by the cyclin-dependent kinase inhibitor p21. J Biol Chem 270: 22008–22016

    Article  PubMed  CAS  Google Scholar 

  • Parker SB, Eichele G, Zhang P, Rawls A, Sands AT, Bradley A, Olson EN, Harper JW, Elledge SJ (1995) p53-independent expression of p2lCipl in muscle and other terminally differentiating cells. Science 267: 1024–1027

    Google Scholar 

  • Petrocelli T, Poon R, Drucker DJ, Slingerland JM, Rosen CF (1996) UVB radiation induces p2lCipl/ WAFT and mediates GI and S phase checkpoints. Oncogene 12: 1387–1396

    PubMed  CAS  Google Scholar 

  • Pietenpol JA, Bohlander SK, Sato Y, Papadopoulos N, Liu B, Friedman C, Trask BJ, Roberts JM, Kinzler KW, Rowley JD et al. (1995) Assignment of the human p27Kipl gene to 12p13 and its analysis in leukemias. Cancer Res 55: 1206–1210

    PubMed  CAS  Google Scholar 

  • Podust VN, Podust LM, Goubin F, Ducommun B, Hubscher U (1995) Mechanism of inhibition of proliferating cell nuclear antigen-dependent DNA synthesis by the cyclin-dependent kinase inhibitor p21. Biochemistry 34: 8869–8875

    Article  PubMed  CAS  Google Scholar 

  • Pollock PM, Pearson JV, Hayward NK (1996) Compilation of somatic mutations of the CDKN2 gene in human cancers:non-random distribution of base substitutions. Genes Chrom Cancer 15: 77–88

    Article  PubMed  CAS  Google Scholar 

  • Polyak K, Kato JY, Solomon MJ, Sherr CJ, Massague J, Roberts JM, Koff A (1994a) p27Kipl, a cyclinCdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest. Genes Dev 8: 9–22

    Google Scholar 

  • Polyak K, Lee MH, Erdjument BH, Koff A, Roberts JM, Tempst P, Massague J (1994b) Cloning of p27Kipl. a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell 78: 59–66

    Article  PubMed  CAS  Google Scholar 

  • Ponce CM, Lee MH, Latres E, Polyak K, Lacombe L, Montgomery K, Mathew S, Krauter K, Sheinfeld J, Massague J, Cordon-Cardo C (1995) p27Kipl: chromosomal mapping to 12p12–12p13.1 and absence of mutations in human tumors. Cancer Res 55: 1211–1214

    Google Scholar 

  • Poon RY, Toyoshima H, Hunter T (1995) Redistribution of the CDK inhibitor p27 between different cyclin-CDK complexes in the mouse fibroblast cell cycle and in cells arrested with lovastatin or ultraviolet irradiation. Mol Biol Cell 6: 1197–1213

    PubMed  CAS  Google Scholar 

  • Reid LH, Crider-Miller SJ, West A, Lee M.-H, Massague J, Weissman BE (1996) Genomic organization of human p57Kip2 gene and its analysis in the G401 Wilm’s tumor assay. Cancer Res 56: 1214–1218

    PubMed  CAS  Google Scholar 

  • Resnitzky D, Hengst L, Reed SI (1995) Cyclin A-associated kinase complex activity is rate limiting for entrance into S phase and is negatively regulated in GI by p27K’°. Mol Cell Biol 15: 4347–4352

    PubMed  CAS  Google Scholar 

  • Reynisdottir I, Polyak K, Iavarone A, Massague J (1995) Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-beta. Genes Dev 9: 1831–1845

    Article  PubMed  CAS  Google Scholar 

  • Russo AA, Jeffrey PD, Patten AK, Massague J, Pavletich NP (1996) Crystal structure of the p27 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex. Nature 382: 325–331

    Article  PubMed  CAS  Google Scholar 

  • Schulze A, Zerfass-Thome K, Berges J, Middendorf S, Jansen-Duerr P, Henglein B (1996) Anchorage-dependent transcription of the cyclin A gene. Mol Cell Biology 16: 4632–4638

    CAS  Google Scholar 

  • Serrano M, Lee H-W, Chin L, Cordon-Cardo C, Beach D, DePinho RA (1996) Role of the INK4a locus in tumor suppression and cell mortality. Cell 85: 27–37

    Article  PubMed  CAS  Google Scholar 

  • Shivji MK, Grey SJ, Strausfeld UP, Wood RD, Blow JJ (1994) Cipl inhibits DNA replication but not PCNA-dependent nucleotide excision-repair. Current Biology 4: 1062–1068

    Article  PubMed  CAS  Google Scholar 

  • Shou W, Dunphy WG (1996) Cell cycle control by Xenopus p28kipa developmentally regulated inhibitor of cyclin dependent kinases. Mol Biol Cell 7: 457–469

    PubMed  CAS  Google Scholar 

  • Skapek SX, Rhee J, Spicer DB, Lassar AB (1995) Inhibition of myogenic differentiation in proliferating myoblasts by cyclin DI-dependent kinase. Science 267: 1022–1024

    Article  PubMed  CAS  Google Scholar 

  • Slingerland JM, Hengst L, Pan CH, Alexander D, Stampfer MR, Reed SI (1994) A novel inhibitor of cyclin-Cdk activity detected in transforming growth factor beta-arrested epithelial cells. Mol Cell Biol 14: 3683–3694

    PubMed  CAS  Google Scholar 

  • Soos TJ, Kiyokawa H, Yan JS, Rubin MS, Giordano A, DeBlasio A, Bottega S, Wong B, Mendelsohn J, Koff A (1996) Formation of p27-Cdk complexes during the human mitotic cell cycle. Cell Growth Diff 7: 135–146

    PubMed  CAS  Google Scholar 

  • Su JY, Rempel RE, Erikson E, Mailer JL (1995) Cloning and characterization of the Xenopus cyclindependent kinase inhibitor p27kip1. Proc Natl Acad Sci USA 92: 10187–10191

    Article  PubMed  CAS  Google Scholar 

  • Sun Y, Hildesheim A, Li H, Li Y, Chen JY, Cheng YI, Hayes RB, Rothman N, Bi WF, Cao Y et al. (1995) No point mutation but a codon 31serarg polymorphism of the WAF-1/CIP-1/p21 tumor suppressor gene in nasopharyngeal carcinoma (NPC): the polymorphism distinguishes Caucasians from Chinese. Cancer Epidemiol Biomarkers Prey 4: 261–267

    CAS  Google Scholar 

  • Takeuchi S, Mori N, Koike M, Slater J, Park S, Miller CW, Miyoshi I, Koeffler, HP (1996) Frequent loss of heterozygosity in region of the KIPI locus in non-small cell lung cancer: evidence for a new tumor suppressor gene on the short arm of chromosome 12. Cancer Res 56: 738–740

    PubMed  CAS  Google Scholar 

  • Toyoshima H, Hunter T (1994) p27, a novel inhibitor of GI cyclin-Cdk protein kinase activity, is related to p21. Cell 78: 67–74

    Google Scholar 

  • Vidal MJ, Loganzo FJ, de Oliveira AR, Hayward NK, Albino AP (1995) Mutations and defective expression of the WAFT p21 tumour-suppressor gene in malignant melanomas. Melanoma Res 5: 243–250

    CAS  Google Scholar 

  • Waga S, Hannon GJ, Beach D, Stillman B (1994) The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 369: 574–578

    Article  PubMed  CAS  Google Scholar 

  • Waldman T, Kinzler KW, Vogelstein B (1995) p21 is necessary for the p53-mediated GI arrest in human cancer cells. Cancer Res 55: 5187–5190

    Google Scholar 

  • Wang QM, Jones JB, Studzinski GP (1996) Cyclin-dependent kinase inhibitor p27 as a mediator of the G1-S phase block induced by 1,25-dihydroxyvitamin D3 in HL60 cells. Cancer Res 56: 264–267

    PubMed  CAS  Google Scholar 

  • Warbrick E. Lane DP, Glover DM, Cox LS (1995) A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21 WAFI and proliferating cell nuclear antigen. Curr Biol 5: 275–282

    Article  PubMed  CAS  Google Scholar 

  • Watanabe H, Fukuchi K, Takagi Y, Tomoyasu S, Tsuruoka N, Gomi K (1995) Molecular analysis of the Cipl/Waft (p21) gene in diverse types of human tumors. Biochim Biophys Acta 1263: 275–280

    PubMed  Google Scholar 

  • Winston J, Dong F, Pledger WJ (1996) Differential modulation of GI cyclins and the Cdk inhibitor p27kip1 by platelet-derived growth factor and plasma factors in density-arrested fibroblasts. J Biol Cheri 271: 11253–11260

    Article  CAS  Google Scholar 

  • Xiong Y, Zhang H, Beach D (1992) D type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA. Cell 71: 505–514

    Article  PubMed  CAS  Google Scholar 

  • Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D (1993a) p21 is a universal inhibitor of cyclin kinases. Nature 366: 701–704

    Google Scholar 

  • Xiong Y, Zhang H, Beach D (1993b) Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation. Genes Dev 7: 1572–1583

    Article  PubMed  CAS  Google Scholar 

  • Zhang H, Xiong Y, Beach, D. (1993) Proliferating cell nuclear antigen and p21 are components of multiple cell cycle kinase complexes. Mol Biol Cell 4: 897–906

    PubMed  CAS  Google Scholar 

  • Zhang H, Hannon GJ, Beach D (1994a) p21-containing cyclin kinases exist in both active and inactive states. Genes Dev 8: 1750–1758

    Article  PubMed  CAS  Google Scholar 

  • Zhang H, Hannon GJ, Casso D, Beach D (1994b) p21 is a component of active cell cycle kinases. Cold Spring Harb Symp Quant Biol 59: 21–29

    PubMed  CAS  Google Scholar 

  • Zhu X, Ohtsubo M, Bohmer RM, Roberts JM, Assoian RK (1996) Adhesion-dependent cell cycle progression linked to the expression of cyclin D1, activation of cyclin E-cdk2, and phosphorylation of the retinoblastoma protein. J Cell Biol 133: 391–403

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Biology, MB-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA

    L. Hengst & S. I. Reed

Authors
  1. L. Hengst
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. I. Reed
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Oncovirology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, SBR7, Rm. SR311, 10550 North Torrey Pines Road, 92037, La Jolla, CA, USA

    Peter K. Vogt Ph.D.

  2. Department of Molecular Medicine, MB-7, The Scripps Research Institute, 10550 North Torrey Pines Road, 92037, La Jolla, CA, USA

    Steven I. Reed Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Hengst, L., Reed, S.I. (1998). Inhibitors of the Cip/Kip Family. In: Vogt, P.K., Reed, S.I. (eds) Cyclin Dependent Kinase (CDK) Inhibitors. Current Topics in Microbiology and Immunology, vol 227. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71941-7_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-71941-7_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-71943-1

  • Online ISBN: 978-3-642-71941-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation