21
Views
98
CrossRef citations to date
0
Altmetric
Cell Growth and Development

Induction of p21WAF1/CIP1 and Inhibition of Cdk2 Mediated by the Tumor Suppressor p16INK4a

, , , , , & show all
Pages 3916-3928 | Received 15 Oct 1998, Accepted 22 Feb 1999, Published online: 28 Mar 2023

REFERENCES

  • Alcorta, D. A., Y. Xiong, D. Phelps, G. Hannon, D. Beach, and J. Barret 1996. Involvement of the cyclin-dependent kinase inhibitor p16INK4a in replicative senescence of normal human fibroblasts. Proc. Natl. Acad. Sci. USA 93:13742–13747.
  • Alevizopoulos, K., J. Vlach, S. Hennecke, and J. Amati 1997. Cyclin E and c-myc promote cell proliferation in the presence of p16INK4a and of hypophosphorylated retinoblastoma family proteins. EMBO J. 16:5322–5333.
  • Ali, A. A., J. N. Marcus, J. P. Harvey, R. Roll, C. P. Hodgson, D. M. Wildrick, A. Chakraborty, and J. Boman 1993. RB1 protein in normal and malignant human colorectal tissue and colon cancer cell lines. FASEB J. 7:931–937.
  • Asamoto, M., T. Hori, H. Baba-Toriyama, M. Sano, S. Takahashi, H. Tsuda, and J. Shirai 1998. p16 gene overexpression in mouse bladder carcinomas. Cancer Lett. 127:9–13.
  • Balbin, M., G. J. Hannon, A. M. Pendas, A. A. Ferrando, F. Vizoso, A. Fueyo, and J. Lopez-Otin 1996. Functional analysis of a p21WAF1/CIP1/SDI1 mutant (Arg94-Trp) identified in a human breast carcinoma. J. Biol. Chem. 271:15782–15786.
  • Baylin, S. B., J. G. Herman, J. R. Graff, P. M. Vertino, and J. Issa 1998. Alterations in DNA methylation: a fundamental aspect of neoplasia. Adv. Cancer Res. 72:141–196.
  • Berns, K., E. M. Hijmans, and J. Bernards 1997. Repression of c-Myc responsive genes in cycling cells causes G1 arrest through reduction of cyclin E/CDK2 kinase activity. Oncogene 15:1347–1356.
  • Blain, S. W., E. Montalvo, and J. Massague 1997. Differential interaction of the cyclin-dependent kinase (Cdk) inhibitor p27Kip1 with cyclin A-Cdk2 and cyclin D2-Cdk4. J. Biol. Chem. 272:25863–25872.
  • Brugarolas, J., R. T. Bronson, and J. Jacks 1998. p21 is a critical CDK2 regulator essential for proliferation control in Rb-deficient cells. J. Cell Biol. 141:503–514.
  • Brugarolas, J., C. Chandrasekaran, J. I. Gordon, D. Beach, T. Jacks, and J. Hannon 1995. Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature 377:552–557.
  • Chen, J., P. Jackson, M. W. Kirschner, and J. Dutta 1995. Separate domains of p21 involved in the inhibition of cdk kinase and PCNA. Nature 374:386–388.
  • Chen, J., P. Saha, S. Kornbluth, B. D. Dynlacht, and J. Dutta 1996. Cyclin-binding motifs are essential for the function of p21CIP1. Mol. Cell. Biol. 16:4673–4682.
  • Chuang, L. S., H. I. Ian, T. W. Koh, H. H. Ng, G. Xu, and J. Li 1997. Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. Science 277:1996–2000.
  • Clurman, B. E., and J. Groudine 1998. The CDKN2A tumor-suppressor locus—a tale of two proteins. N. Engl. J. Med. 338:910–912.
  • Dai, C. Y., and G. H. Enders. Unpublished data.
  • DeGregori, J., T. Kowalik, and J. Nevins 1995. Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes. Mol. Cell. Biol. 15:4215–4224.
  • Deng, C., P. Zhang, J. W. Harper, S. J. Elledge, and J. Leder 1995. Mice lacking p21Cip1/WAF1 undergo normal development, but are defective in G1 checkpoint control. Cell 82:675–684.
  • de Nooij, J. C., M. A. Letendre, and J. Hariharan 1996. A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila embryogenesis. Cell 87:1237–1247.
  • Dulic, V., E. Lees, and J. Reed 1992. Association of human cyclin E with a periodic G1-S phase protein kinase. Science 257:1958–1961.
  • Duro, D., O. Bernard, V. Della Valle, R. Berger, and J. Larsen 1995. A new type of p16INK4/MTS1 gene transcript expressed in B-cell malignancies. Oncogene 11:21–29.
  • Dyson, N. 1994. pRB, p107, and the regulation of the E2F transcription factor. J. Cell Sci. Suppl. 18:81–87.
  • El-Deiry, W. S. 1998. p21/p53, cellular growth control, and genomic integrity. Curr. Top. Microbiol. Immunol. 227:121–137.
  • El-Deiry, W. S., T. Tokino, V. E. Velculescu, D. B. Levy, R. Parsons, J. M. Trent, D. Lin, W. E. Mercer, K. W. Kinzler, and J. Vogelstein 1993. WAF1, a potential mediator of p53 tumor suppression. Cell 75:817–825.
  • Enders, G. H., D. Ganem, and J. Varmus 1987. 5′-Terminal sequences influence the segregation of ground squirrel hepatitis virus RNAs into polyribosomes and viral core particles. J. Virol. 61:35–41.
  • Enders, G. H., J. Koh, C. Missero, A. K. Rustgi, and J. Harlow 1996. p16 inhibition of transformed and primary squamous epithelial cells. Oncogene 12:1239–1245.
  • Ewen, M. E., C. J. Oliver, H. K. Sluss, S. J. Miller, and J. Peeper 1995. p53-dependent repression of CDK4 translation in TGF-β-induced G1 cell-cycle arrest. Genes Dev. 9:204–217.
  • Fahraeus, R., J. M. Paramio, K. L. Ball, S. Lain, and J. Lane 1996. Inhibition of pRb phosphorylation and cell-cycle progression by a 20-residue peptide derived from p16CDKN2/INK4A. Curr. Biol. 6:84–91.
  • Fero, M. L., M. Rivkin, M. Tasch, P. Porter, C. E. Carow, E. Firpo, K. Polyak, L. H. Tsai, V. Broudy, R. M. Perlmutter, K. Kaushansky, and J. Roberts 1996. A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27Kip1-deficient mice. Cell 85:733–744.
  • Foster, S. A., D. J. Wong, M. T. Barrett, and J. Galloway 1998. Inactivation of p16 in human mammary epithelial cells by CpG island methylation. Mol. Cell. Biol. 18:1793–1801.
  • Funk, J. O., S. Waga, J. B. Harry, E. Espling, B. Stillman, and J. Galloway 1997. Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein. Genes Dev. 11:2090–2100.
  • Geradts, J., and J. Wilson 1996. High frequency of aberrant p16INK4A expression in human breast carcinoma. Am. J. Pathol. 149:15–20.
  • Gossen, M., and J. Bujard 1992. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc. Natl. Acad. Sci. USA 89:5547–5551.
  • Graham, F. L., and J. Prevec 1995. Methods for construction of adenovirus vectors. Mol. Biotechnol. 3:207–220.
  • Gray-Bablin, J., S. Rao, and J. Keyomarsi 1997. Lovastatin induction of cyclin-dependent kinase inhibitors in human breast cells occurs in a cell cycle-independent fashion. Cancer Res. 57:604–609.
  • Gudas, J., H. Nguyen, T. Li, D. Hill, and J. Cowan 1995. Effects of cell cycle, wild-type p53 and DNA damage on p21CIP1/Waf1 expression in human breast epithelial cells. Oncogene 11:253–261.
  • Haber, D. 1997. Splicing into senescence: the curious case of p16 and p19ARF. Cell 91:555–558.
  • Hara, E., R. Smith, D. Parry, H. Tahara, S. Stone, and J. Peters 1996. Regulation of p16CDKN2 expression and its implications for cell immortalization and senescence. Mol. Cell. Biol. 16:859–867.
  • Harada, N., S. Gansauge, F. Gansauge, H. Gause, S. Shimoyama, T. Imaizumi, T. Mattfeld, M. Schoenberg, and J. Beger 1997. Nuclear accumulation of p53 correlates significantly with clinical features and inversely with the expression of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 in pancreatic cancer. Br. J. Cancer 76:299–305.
  • Harlow, E., D. Lane 1988. Antibodies: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
  • Helin, K., and J. Harlow 1993. The retinoblastoma protein as a transcriptional repressor. Trends Cell Biol. 3:43–46.
  • Hengst, L., and J. Reed 1996. Translation control of p27KIP1 accumulation during the cell cycle. Science 271:1861–1864.
  • Herman, J. G., A. Merlo, R. G. Lapidus, J.-P. Issa, N. E. Davidson, D. Sidransky, and J. Baylin 1995. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res. 55:4525–4530.
  • Horowitz, J. M., S. H. Park, E. Bogenmann, J. C. Cheng, D. W. Yandell, F. J. Kaye, J. D. Minna, T. P. Dryja, and J. Weinberg 1990. Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumor cells. Proc. Natl. Acad. Sci. USA 87:2775–2779.
  • Jiang, H., H. S. Chou, and J. Zhu 1998. Requirement of cyclin E-Cdk2 inhibition in p16INK4a-mediated growth suppression. Mol. Cell. Biol. 18:5284–5290.
  • Jones, D. L., R. M. Alani, and J. Munger 1997. The human papillomavirus E7 oncoprotein can uncouple cellular differentiation and proliferation in human keratinocytes by abrogating p21Cip1-mediated inhibition of cdk2. Genes Dev. 11:2101–2111.
  • Kamb, A., D. Shattuck-Eidens, R. Eeles, Q. Liu, N. A. Gruis, W. Ding, C. Hussey, T. Tran, Y. Miki, J. Weaver-Feldhaus, M. McClure, J. F. Aitken, D. E. Anderson, W. Bergman, R. Frants, D. E. Goldgar, A. Green, R. MacLennan, N. G. Martin, L. J. Meyer, P. Youl, J. J. Zone, M. H. Scolnick, and J. Cannon-Albright 1994. Analysis of the p16 gene (cdkN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nat. Genet. 8:22–26.
  • Kamb, A., N. A. Gruis, J. Weaver-Feldhaus, Q. Liu, K. Harshman, S. V. Tavtigian, E. Stockert, R. S. Day, B. E. Johnson, and J. Skolnick 1994. A cell cycle regulator potentially involved in genesis of many tumor types. Science 264:436–440.
  • Kamijo, T., F. Zindy, M. F. Roussel, D. E. Quelle, J. R. Downing, R. A. Ashburn, G. Grosveld, and J. Sherr 1997. Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell 91:649–660.
  • Kato, D., K. Miyazawa, M. Ruas, M. Starborg, I. Wada, T. Oka, T. Sakai, G. Peters, and J. Hara 1998. Features of replicative senescence induced by direct addition of antennapedia-p16INK4A fusion protein to human diploid fibroblasts. FEBS Lett. 427:203–208.
  • Keyomarsi, K., L. Sandoval, V. Band, and J. Pardee 1991. Synchronization of tumor and normal cells from G1 to multiple cell cycles by lovastatin. Cancer Res. 51:3602–3609.
  • Kiyokawa, H., R. D. Kineman, K. O. Manova-Todorova, V. C. Soares, E. S. Hoffman, M. Ono, D. Khanam, A. C. Hayday, L. A. Frohman, and J. Koff 1996. Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27Kip1. Cell 85:721–732.
  • Knoblich, J., K. Sauer, L. Jones, H. Richardson, R. Saint, and J. Lehner 1994. Cyclin E controls S phase progression and its down-regulation during Drosophila embryogenesis is required for the arrest of cell proliferation. Cell 77:107–120.
  • Koh, J., G. H. Enders, B. D. Dynlacht, and J. Harlow 1995. Tumor-derived p16 alleles encoding proteins defective in cell cycle inhibition. Nature 375:506–510.
  • LaBaer, J., M. D. Garret, L. F. Stevenson, J. M. Slingerland, C. Sandhu, H. S. Chou, A. Fattaey, and J. Harlow 1997. New functional activities for the p21 family of cdk inhibitors. Genes Dev. 11:847–862.
  • Lane, M. E., K. Sauer, K. Wallace, Y. N. Jan, C. F. Lehner, and J. Vaessin 1996. Dacapo, a cyclin-dependent kinase inhibitor, stops cell proliferation during Drosophila development. Cell 87:1225–1235.
  • Lees, E., B. Faha, V. Dulic, S. I. Reed, and J. Harlow 1992. Cyclin E/cdk2 and cyclin A/cdk2 kinases associate with p107 and E2F in a temporally distinct manner. Genes Dev. 6:1874–1885.
  • Liggett, W. H. Jr., D. A. Sewell, J. Rocco, S. A. Ahrendt, W. Koch, and J. Sidransky 1996. p16 and p16 beta are potent growth suppressors of head and neck squamous carcinoma cells in vitro. Cancer Res. 56:4119–4123.
  • Lukas, J., T. Herzinger, K. Hansen, M. C. Moroni, D. Resnitzky, K. Helin, S. I. Reed, and J. Bartek 1997. Cyclin E-induced S phase without activation of the pRB/E2F pathway. Genes Dev. 11:1479–1492.
  • Lukas, J., D. Parry, L. Aagaard, D. J. Mann, J. Bartkova, M. Strauss, G. Peters, and J. Bartek 1995. Retinoblastoma-protein-dependent inhibition by the tumor-suppressor p16. Nature 375:503–506.
  • Lundberg, A. S., and J. Weinberg 1998. Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. Mol. Cell. Biol. 18:753–761.
  • Luo, Y., J. Hurwitz, and J. Massague 1995. Cell-cycle inhibition by independent CDK and PCNA binding domains in p21Cip1. Nature 375:159–161.
  • Malkowicz, S. B., J. E. Tomaszewski, A. J. Linnenbach, T. A. Cangiano, Y. Maruta, and J. McGarvey 1996. Novel p21WAF1/CIP1 mutations in superficial and invasive transitional cell carcinomas. Oncogene 13:1831–1837.
  • Mann, D. J., and J. Jones 1996. E2F-1 but not E2F-4 can overcome p16-induced G1 cell cycle arrest. Curr. Biol. 6:474–483.
  • Mao, L., A. Merlo, G. Bedi, G. I. Shapiro, C. D. Edwards, B. J. Rollins, and J. Sidransky 1995. A novel p16INK4A transcript. Cancer Res. 55:2995–2997.
  • Mathews, M., N. Sonnenburg, and J. Hershey 1996. Origins and targets of translational control In J. Hershey, M. Mathews, N. Sonnenburg (ed.), Translational control, 2nd ed. 1:1–29 Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
  • McConnell, B. B., F. J. Gregory, F. J. Stott, E. Hara, and J. Peters 1999. Induced expression of p16INK4a inhibits both CDK4- and CDK2-associated kinase activity by reassortment of cyclin-CDK-inhibitor complexes. Mol. Cell. Biol. 19:1981–1989.
  • McConnell, B. B., M. Starborg, S. Brookes, and J. Peters 1998. Inhibitors of cyclin-dependent kinases induce features of replicative senescence in early passage human diploid fibroblasts. Curr. Biol. 8:351–354.
  • Medema, R. H., R. E. Herrera, F. Lam, and J. Weinberg 1995. Growth suppression by p16ink4 requires functional retinoblastoma protein. Proc. Natl. Acad. Sci. USA 92:6289–6293.
  • Meyerson, M., and J. Harlow 1994. Identification of G1 kinase activity for cdk6, a novel cyclin D partner. Mol. Cell. Biol. 14:2077–2086.
  • Millard, S. S., J. S. Yan, H. Nguyen, M. Pagano, H. Kiyokawa, and J. Koff 1997. Enhanced ribosomal association of p27Kip1 mRNA is a mechanism contributing to accumulation during growth arrest. J. Biol. Chem. 272:7093–7098.
  • Missero, C., F. Di Cunto, H. Kiyokawa, A. Koff, and J. Dotto 1996. The absence of p21Cip1/WAF1 alters keratinocyte growth and differentiation. Genes Dev. 10:3065–3075.
  • Mitra, J., and G. H. Enders. Unpublished data.
  • Myohanen, S. K., S. B. Baylin, and J. Herman 1998. Hypermethylation can selectively silence individual p16ink4A alleles in neoplasia. Cancer Res. 58:591–593.
  • Nakayama, K., N. Ishida, M. Shirane, A. Inomata, T. Inoue, N. Shishido, I. Horii, and J. Loh 1996. Mice lacking p27Kip1 display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors. Cell 85:707–720.
  • Nobori, T., K. Miura, D. J. Wu, A. Lois, K. Takabayashi, and J. Carson 1994. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 368:753–756.
  • Noda, A., Y. Ning, S. F. Venable, O. M. Pereira-Smith, and J. Smith 1994. Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp. Cell Res. 211:90–98.
  • Ohtsubo, M., A. M. Theodoras, J. Schumacher, J. M. Roberts, and J. Pagano 1995. Human cyclin E, a nuclear protein essential for the G1-to-S phase transition. Mol. Cell. Biol. 15:2612–2624.
  • Polyak, K., M.-H. Lee, H. Erdjument-Bromage, A. Koff, J. M. Roberts, P. Tempst, and J. Massague 1994. Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell 78:59–66.
  • Polymenis, M., and J. Schmidt 1997. Coupling of cell division to cell growth by translational control of the G1 cyclin CLN3 in yeast. Genes Dev. 11:2522–2531.
  • Pomerantz, J., N. Schreiber-Agus, N. J. Liegeois, A. Silverman, L. Alland, L. Chin, J. Potes, K. Chen, I. Orlow, H. W. Lee, C. Cordon-Cardo, and J. DePinho 1998. The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2’s inhibition of p53. Cell 92:713–723.
  • Poon, R. Y. C., and J. Hunter 1995. Dephosphorylation of Cdk2 Thr-160 by the cyclin-dependent kinase-interacting phosphatase KAP in the absence of cyclin. Science 270:90–93.
  • Quelle, D. E., M. Cheng, R. A. Ashmun, and J. Sherr 1997. Cancer-associated mutations at the INK4a locus cancel cell cycle arrest by p16INK4a but not by the alternative reading frame protein p19ARF. Proc. Natl. Acad. Sci. USA 94:669–673.
  • Quelle, D. E., F. Zindy, R. A. Ashmun, and J. Sherr 1995. Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest. Cell 83:993–1000.
  • Reynisdottir, I., and J. Massague 1997. The subcellular locations of p15Ink4b and p27Kip1 coordinate their inhibitory interactions with cdk4 and cdk2. Genes Dev. 11:492–503.
  • Reynisdottir, I., K. Polyak, A. Iavarone, and J. Massague 1995. Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-β. Genes Dev. 9:1831–1845.
  • Reznikoff, C. A., T. R. Yeager, C. D. Belair, E. Savelia, J. A. Puthenveetil, and J. Stadler 1996. Elevated p16 at senescence and loss of p16 at immortalization in human papillomovirus 16 E6, but not E7, transformed human uroepithelial cells. Cancer Res. 56:2886–2890.
  • Robertson, K. D., and J. Jones 1998. The human ARF cell cycle regulatory gene promoter is a CpG island which can be silenced by DNA methylation and down-regulated by wild-type p53. Mol. Cell. Biol. 18:6457–6473.
  • Rogan, E. M., T. M. Bryan, B. Hukku, K. Maclean, A. C.-M. Chang, E. L. Moy, A. Englezou, S. G. Warneford, L. Dalla-Pozza, and J. Reddel 1995. Alterations in p53 and p16INK4 expression and telomere length during spontaneous immortalization of Li-Fraumeni syndrome fibroblasts. Mol. Cell. Biol. 15:4745–4753.
  • Rogatsky, I., J. M. Trowbridge, and J. Garabedian 1997. Glucocorticoid receptor-mediated cell cycle arrest is achieved through distinct cell-specific transcriptional regulatory mechanisms. Mol. Cell. Biol. 17:3181–3193.
  • Royzman, I., A. J. Whittaker, and J. Orr-Weaver 1997. Mutations in Drosophila DP and E2F distinguish G1-S progression from an associated transcriptional program. Genes Dev. 11:1999–2011.
  • Russo, A., L. Tong, J.-O. Lee, P. Jeffrey, and J. Pavletich 1998. Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a. Nature 395:237–243.
  • Russo, A. A., P. D. Jeffrey, A. K. Patten, J. Massague, and J. Pavletich 1996. Crystal structure of the p27Kip1 cyclin dependent kinase inhibitor bound to the cyclin A-Cdk2 complex. Nature 382:325–331.
  • Sambrook, J., E. Fritsch, T. Maniatis 1989. Molecular cloning: a laboratory manual, 2nd ed. 1: Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
  • Sandig, V., K. Brand, S. Herwig, J. Lukas, J. Bartek, and J. Strauss 1997. Adenovirally transferred p16INK4/CDKN2 and p53 cooperate to induce apoptotic tumor cell death. Nat. Med. 3:313–319.
  • Satyamoorthy, K., M. Nesbit, M.-Y. Hsu, M. Herlyn 1996. Utility of adenoviruses as gene expression modules in melanoma, p. 71–77. In M. Maio (ed.), Immunology of human melanoma. IOS Press, Amsterdam, The Netherlands.
  • Satyamoorthy, K., P. W. Soballe, F. Soans, and J. Herlyn 1997. Adenovirus infection enhances killing of melanoma cells by a mitotoxin. Cancer Res. 57:1873–1876.
  • Serrano, M., E. Gomez-Lahoz, R. A. DePinho, D. Beach, and J. Bar-Sagi 1995. Inhibition of ras-induced proliferation and cellular transformation by p16INK4. Science 267:249–252.
  • Serrano, M., G. J. Hannon, and J. Beach 1993. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366:704–707.
  • Sewing, A., B. Wiseman, A. C. Lloyd, and J. Land 1997. High-intensity Raf signal causes cell cycle arrest mediated by p21Cip1. Mol. Cell. Biol. 17:5588–5597.
  • Sherr, C. J. 1996. Cancer cell cycles. Science 274:1672–1677.
  • Soos, T. J., H. Kiyokawa, J. S. Yan, M. S. Rubin, A. Giordano, A. DeBlasio, S. Bottega, B. Wong, J. Mendelsohn, and J. Koff 1996. Formation of p27-CDK complexes during the human mitotic cell cycle. Cell Growth Differ. 7:135–146.
  • Stone, S., P. Jiang, P. Dayananth, S. V. Tavtigian, H. Katcher, D. Parry, G. Peters, and J. Kamb 1995. Complex structure and regulation of the P16 (MTS1) locus. Cancer Res. 55:2988–2994.
  • Tsai, L.-H., E. Lees, B. Faha, E. Harlow, and J. Riabowol 1993. The cdk2 kinase is required for the G1-to-S transition in mammalian cells. Oncogene 8:1593–1602.
  • Uhrbom, L., M. Nister, and J. Westermark 1997. Induction of senescence in human malignant glioma cells by p16INK4A. Oncogene 15:505–514.
  • van den Heuvel, S., and J. Harlow 1993. Distinct roles for cyclin-dependent kinases in cell cycle control. Science 262:2050–2054.
  • Waldman, T., K. W. Kinzler, and J. Vogelstein 1995. p21 is necessary for the p53-mediated G1 arrest in human cancer cells. Cancer Res. 55:5187–5190.
  • Wang, J., and J. Walsh 1996. Resistance to apoptosis conferred by Cdk inhibitors during myocyte differentiation. Science 273:359–361.
  • Weinberg, R. A. 1995. The retinoblastoma protein and cell cycle control. Cell 81:323–330.
  • Wu, C.-L., M. Classon, N. Dyson, and J. Harlow 1996. Expression of dominant-negative mutant DP-1 blocks cell cycle progression in G1. Mol. Cell. Biol. 16:3698–3706.
  • Xiao, Z.-H., D. Ginsberg, M. Ewen, and J. Livingston 1996. Regulation of the retinoblastoma protein-related protein p107 by G1 cyclin-associated kinases. Proc. Natl. Acad. Sci. USA 93:4633–4637.
  • Xiong, Y., H. Zhang, and J. Beach 1993. Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation. Genes Dev. 7:1572–1583.
  • Zhang, H., G. J. Hannon, and J. Beach 1994. p21-containing cyclin kinases exist in both active and inactive states. Genes Dev. 8:1750–1758.
  • Zhang, Y., Y. Xiong, and J. Yarbrough 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.
  • Zindy, F., C. Eischen, D. Randle, T. Kamijo, J. Cleveland, C. Sherr, and J. Roussel 1998. Myc signalling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization. Genes Dev. 12:2424–2433.
  • Zindy, F., D. E. Quelle, M. F. Roussel, and J. Sherr 1997. Expression of the p16INK4a tumor suppressor versus other INK4 family members during mouse development and aging. Oncogene 15:203–211.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.