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研究生:林緯
論文名稱:CDKIp21促使細胞生長停滯和抑制氫化刺激引起之細胞凋零的機制
論文名稱(外文):Transduced CDKI p21 induces growth arrest and inhibits apoptosis elicited by oxidative stress
指導教授:唐世杰
學位類別:碩士
校院名稱:國立海洋大學
系所名稱:水產生物技術研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:68
中文關鍵詞:細胞生長停滯細胞凋零
外文關鍵詞:apoptosisCDKCDKIoxidative stressp21
相關次數:
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  • 下載下載:20
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中文摘要
阿茲海默症主要起因於常駐在腦中的microglial cell,在腦部受到傷害或是產生發炎反應時會被活化且異常增生,活化後藉由Reactive oxygen species(ROS)的產生而誘導出一系列signal transduction cascade最終導致細胞的死亡而導致neurodegeneration(神經退化現象)。細胞的生長必須順著細胞週期依序的前進,而CDKs在細胞週期中即是扮演著細胞通過每一相(phase)的調控者。而CDKs它則會受到cyclin dependent kinase inhibitors(CDKIs)的抑制而失去其kinase activity,而導致細胞週期無法繼續向前進行。
本次實驗發現以TAT- protein transduction的方式將TAT-p21送入BV-2 microglial cells能有效抑制BV-2的生長力。並且提供BV-2能抵抗ROS所誘導之細胞凋零的能力。

Abstract
Microglials are resident monocyte-lineaged cells in the brain. Their characteristic feature is that they react to injury and diseases of the brain and become functionally activated and generates (ROS) reactive oxygen species. Reactive oxygen species play an important role in apoptosis under microglial cells activated.
Progression through the cell cycle is regulated by cyclins and cyclin-dependent kinases (CDK). The cyclin inhibitor p21 can induce G1 arrest and block entry into S phase by inactivating CDKs.
We conciude that transduction of TAT-p21 into cells resulted in the loss of CDK kinase activity, elicited an G1 cell cycle arrest, and inhibited apoptosis elicited by oxidative stress.

目 錄
壹、 序 論……………………………………………......1
貳、 材 料..……………………………………………... 12
參、 方 法………………………………………………... 15
肆、 結 果………………………………………………... 28
伍、 討 論………………………………………………... 34
陸、 附 圖………………………………………………... 38
柒、 參考文獻……………………………………………... 61

柒、參考文獻
Akashi, M., Hachiya, M., Osawa, Y., Spirin, K., Suzuki, G., Koeffler, H. P. 1995. Irradiation induced WAF1 expression through a p53-independent pathway in KG-1 cells. J. Biol. Chem. 270: 19181-19187.
Aktas, H., H. Cai, and G.M. Cooper. 1997. Ras links growth factor signaling to the cell cycle machinery via regulation of cyclin D1 and the cdk inhibitor p27Kip1. Mol. Cell. Biol.17: 3850—3857.
Albanese, C., J. Johnson, G. Watanabe, N. Eklund, D. Vu, A. Arnold, and R.G. Pestell. 1995. Transforming p21ras mutants and c-Ets-2 activate the cyclin D1 promoter through distinguishable regions. J. Biol. Chem. 270: 23589—23597.
Ashkenazi, A., Dixit, V. M. 1998. Death receptors:Signaling and modulation. Science. 281:1305-1308.
Bae, I., Fan, S., Bhatia, K., Kohn K. W., Fornace A. J., O’Connor, P. M. 1995. Relationships between G1 arrest and stability of p53 and p21 Cip1/Waf1 proteins following gamma-irraditation of human lymphoma cells. Cancer Res. 5585:2387-2393.
Bellido, T., O’Brien, C. A., Roberson, P. K., Manolagas, S. C. 1998. Transcriptional activation of the p21(WAF1, CIP1, SDI1) gene by interleukin-6 type cytokines. A prerequisite for their pro-differentiating and anti-apoptotic effects on human osteoblastic cells. J. Biol. Chem. 273: 21137-21144.
Chan, F.K.M., J. Zhang, L. Chen, D.N. Shapiro, and A. Winoto. 1995. Identification of human/mouse p19, a novel CDK4/CDK6 inhibitor with homology to p16ink4. Mol. Cell. Biol. 15: 2682—2688.
Chedid, M., Michieli, P., Lengel, C., Huppi, K., Givol, D. 1994. A single nucleotide substitution at codon 31(Ser/Arg)defines a polymorphism in a highly conserved region of the p53-inducuble gene WAF1/CIP1. Oncogene. 9:3021-3024.
Chen, J., P. Saha, S. Kornbluth, B.D. Dynlacht, and A. Dutta. 1996. Cyclin-binding motifs are essential for the function of p21Cip1. Mol. Cell. Biol. 16: 4673—4682.
Chen, J., P.K. Jackson, M.W. Kirschner, and A. Dutta. 1995. Separate domains of p21 involved in the inhibition of cdk kinase and PCNA. Nature 374: 386—388.
Cheng, M., P. Olivier, J.A. Diehl, M. Fero, M.F. Roussel, J.M. Roberts, and C.J. Sherr. 1999. The p21Cip1 and p27Kip1 CDK ‘inhibitors’ are essential activators of cyclin D-dependent kinases in murine fibroblasts. EMBO J. 18: 1571—1583.
Chiba, T., Takahashi, S., Sato, N., Ishii, S., Kikuchi, K. 1996. Fas-mediated apoptosis is modulated by intracellular glutathione in human T cells. Eur. J. Immunol. 26:1164-1169.
Chinery, R., Brockman, J. A., Peeler, M. O., Shyr, Y., Beauchamp, R. D., Coffey, R. J. 1997. Antioxidants enhance the cytotoxicity of chemotherapeutic agents in colorectal cancer: A p53-independent induction of p21WAF1/CIP1 via C/EBPβ. Nat. Med. 3: 1233-1241.
Cossarizza, A., Franeschi, C., Monti, D. 1995. Protective effect of N-acetylcysteine in tumor necrosis factor-alpha-induced apoptosis in U937 cells:The role of mitochondria. Exp. Cell Res. 220:232-240.
Dibbert. B., Weber, M., Nikolaizik, W. H. 1999. Cytokine-mediated Bax deficiency and consequent delayed neutrophil apoptosis:A general mechanism to acculate effector cells in inflammation. Proc. Natl. Acdd. Sci. USA 96:13330-13335.
Dulic, V., W.K. Kaufmann, S.J. Wilson, T.D. Tlsty, E. Lees, J.W. Harper, S.J. Elledge, and S.I. Reed. 1994. p53-Dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest. Cell 76: 1013—1023.
Dulic, V., W.K. Kaufmann, S.J. Wilson, T.D. Tlsty, E. Lees, J.W. Harper, S.J. Elledge, and S.I. Reed. 1994. p53-Dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest. Cell 76: 1013—1023.
El-Deiry, W. S., Tokino, T., Waldman, T., Oliner, J. D., Velculescu, V. E., Burrell, M., Hill, D. E., Healy, E., Rees, J. L., Hamilton, S. R. 1995. Topological control of p21WAF1/CIP1 expression in normal and neoplastic tissues. Cancer Res. 55: 2910-2919.
El-Deiry, W.S., T. Tokino, V.E. Velculescu, D.B. Levy, R. Parsons, J.M. Trent, D. Lin, E. Mercer, K.W. Kinzler, and B. Vogelstein. 1993. WAF1, a potential mediator of p53 tumor suppression. Cell 75: 817—825.
Esposito, F., Cuccovillo, F., Vanoni, M., Cimino, F., Anderson, C. W., Appella, E., Russo, T. 1997. Redox-mediated regulation of p21WAF1/CIP1 expression involved a post transcriptional mechanism and activation of the mitogen-activated protein kinase pathway. Eur. J. Biochem. 245: 730-737.
Ezhevsky, S.A., H. Nagahara, A.M. Vocero-Akbani, D.R. Gius, M.C. Wei, and S.F. Dowdy. 1997. Hypo-phosphorylation of the retinoblastoma protein (pRb) by cyclin D:Cdk4/6 complexes results in active pRb. Proc. Natl. Acad. Sci.94: 10699—10704.
Fawell S. 1994. TAT-mediated delivery of heterologous proteins into cells. Proc. Natl Acad Sci USA. 91: 664-668.
Filmus, J., A.I. Robles, W. Shi, M.J. Wong, L.L. Colombo, and C.J. Conti. 1994. Induction of cyclin D1 overexpression by activated ras. Oncogene 9: 3627—3633.
Frankel, A., Pabo, C. O. 1988. Cellular uptake of the tat protein from human immunodeficiency virus. Cell. 55:1189-1193.
Gorospe, M., Martindale, J. M., Sheikh, M. S., Fornace, A. J. Jr., Holbrook, N. J. 1996. Regulation of p21WAF1/CIP1 expression by cellular stress: p53-dependent and —independent mechanisms. Mol. Cell. Differ. 4: 47-65.
Green, M., Loewenstein, P. M. 1988. Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein. Cell. 55:1179-1188.
Gu, Y., C.W. Turek, and D.O. Morgan. 1993. Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit. Nature 366: 707—710.
Hannon, G.J. and D. Beach. 1994. p15INK4b is a potential effector of TGFβ-induced cell cycle arrest. Nature 371: 257—261.
Harper, J.W., G.R. Adami, N. Wei, K. Keyomarsi, and S.J. Elledge. 1993. The p21 cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 75: 805—816.
Harper, J.W., S.J. Elledge, K. Keyomarsi, B. Dynlacht, L.H. Tsai, P. Zhang, S. Dobrowolski, C. Bai, L. Connell-Crowley, E. Swindell, M.P. Fox, and N. Wei. 1995. Inhibition of cyclindependent kinases by p21. Mol. Biol. Cell 6: 387—400.
Hebestreit, H., Dibbert, B., Balatti, I. 1998. Disruption of Fas receptor signaling by nitric oxide in eosinophils. J. Exp. Med. 187:415-425.
Hirai, H., M.F. Roussel, J. Kato, R.A. Ashmun, and C.J. Sherr. 1995. Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6. Mol. Cell. Biol. 15: 2672—2681.
Hobeika, A. C., Subramaniam, P. S., Johnson, H. M. 1997. INFα induces the expression of the cyclin-dependent kinase inhibitor p21 in human prostate cancer cells. Oncogene 14: 1165-1170.
Kerkhoff, E. and U.R. Rapp. 1997. Induction of cell proliferation in quiescent NIH 3T3 cells by oncogenic c-Raf-1. Mol. Cell. Biol. 17: 2576—2586.
Kitagawa, M., H. Higashi, H.K. Jung, I. Suzuki-Takahashi, M. Ikeda, K. Tamai, J. Kato, K. Segawa, E. Yoshida, S. Nishimura, and Y. Taya. 1996. The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2. EMBO J. 15: 7060—7069.
Koh, J., G.H. Enders, B.D. Dynlacht, and E. Harlow. 1995. Tumour- derived p16 alleles encoding proteins defective in cell cycle inhibition. Nature 375: 506—510.
Krammer, P. H. 1999. CD95(APO-1/Fas)-mediated apoptosis:Live and let die. Adv. Immunol. 71:163-210.
Lavoie, J.N., G. L’Allemain, A. Brunet, R. Mu¨ ller, and J. Pouysse ´gur. 1996. Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway. J. Biol. Chem. 271: 20608—20616.
Law, J. C., Deka, A. 1995. Identification of a Pst1 polymorphism in the p21Cip1/Waf1 cyclin-dependent kinase inhibitor gene. Hum. Genet. 95:459-460.
Lee, M.H., I. Reynisdo´ ttir, and J. Massague´ . 1995. Cloning of p57Kip2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Genes&Dev. 9: 639—649.
Li, Y. J., Laurent-Puig, P., Salmon, R. J., Thomas, G., Hamelin, R. 1995. Polymorphisms and probable lack of mutation in the WAF1/CIP1 gene in colorectal cancer. Oncogene. 10:599-601.
Lin, J., C. Reichner, X. Wu, and A.J. Levine. 1996. Analysis of wild-type and mutant p21WAF-1 gene activities. Mol. Biol. Cell 16: 1786—1793.
Liu, B., Andrieu Abadie, N., Levade, T., Zhang, P., Obeid, L. M., Hannum, Y. A. 1998. Glutathione regulation of neutral sphingomyelinase in tumor necrosis factor-alpha-induced cell death. J. Biol. Chem. 273:11313-11320.
Ludlow, J.W., C.L. Glendening, D.M. Livingston, and J.A. De-Caprio. 1993. Specific enzymatic dephosphorylation of the retinoblastoma protein. Mol. Cell. Biol. 13: 367—372.
Ludlow, J.W., J. Shon, J.M. Pipas, D.M. Livingston, and J.A. De-Caprio. 1990. The retinoblastoma susceptibility gene product undergoes cell cycle-dependent dephosphorylation and binding to and release from SV40 large T. Cell 60: 387—396.
Lukas, J., J. Bartkova, M. Rohde, M. Strauss, and J. Bartek. 1995a. Cyclin D1 is dispensable for G1 control in retinoblastoma gene-deficient cells, independent of CDK4 activity.Mol. Cell. Biol. 15: 2600—2611.
Lundberg, A.S. and R.A. 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.
Macleod, K. F., Sherry, N., Hannon, G., Beach, D., Tokino, T., Kinzler, K., Vogelstein B., Jack, T. 1995. p53-dependent and independent expression of p21 during cell growyh, differentiation, and DNA damage. Genes & Dev. 9: 935-944.
Mann, D. A., Frankel, A. D. 1991. Endocytosis and targeting of exogenous HIV-1 TAT. EMBO J. 10:1733-1739.
Matsumura, I., Ishikawa, J., Nakajima, K., Oritani, K., Tomiyama, Y., Kanakura, Y. 1997. Thrombopoietin-induced differentiation of a human megakaryoblastic leukemia cell line, CMK, involves transcriptional activation of p21(WAF1/CIP1)by STAT5. Mol. Cell. Biol. 17: 2933-2943.
Matsuoka, S., M. Edwards, C. Bai, S. Parker, P. Zhang, A. Baldini, J.W. Harper, and S.J. Elledge. 1995. p57KIP2, a structurally distinct member of the p21CIP1 cdk inhibitor family, is a candidate tumor suppressor gene. Genes & Dev. 9: 650—662.
Matsushime, H., D.E. Quelle, S.A. Shurtleff, M. Shibuya, C.J. Sherr, and J.-Y. Kato. 1994. D-type cyclin-dependent kinase activity in mammalian cells. Mol. Cell. Biol. 14: 2066—2076.
McConnell, B.B., F.J. Gregory, F.J. Stott, E. Hara, and G. 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.
Medema, R.H., R.E. Herrera, F. Lam, and R.A. Weinberg. 1995. Growth suppression by p16ink4 requires functional retinoblastoma protein. Proc. Natl. Acad. Sci. 92: 6289—6293.
Meyerson, M. and E. Harlow. 1994. Identification of a G1 kinase activity for cdk6, a novel cyclin D partner. Mol. Cell. Biol.14: 2077—2086.
Mittnacht, S., J.A. Lees, D. Desai, E. Harlow, D.O. Morgan, and R.A. Weinberg. 1994. Distinct sub-populations of the retinoblastoma protein show a distinct pattern of phosphorylation. EMBO J. 13: 118—127.
Mousses, S., Ozcelik, H., Lee, P. D., Malkin, D., Bull, S. B. Andrulis, I. L. 1995. Two variants of the human cancer. Hum. Mol. Genet. 4:1089-1092.
Nakanishi, M., R.S. Robetorge, G.R. Adami, O.M. Pereira-Smith, and J.R. Smith. 1995. Identification of the active region of the DNA synthesis inhibitory gene p21Sdi1/CIP1/WAF1. EMBO J. 14: 555—563.
Noda, A., Y. Ning, S.F. Venable, O.M. Pereira-Smith, and J.R. Smith. 1994. Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp. Cell. Res.211: 90—98.
Parry, D., S. Bates, D.J. Mann, and G. Peters. 1995. Lack of cyclin D-cdk complexes in Rb-negative cells correlates with high levels of p16INK4/MTS1 tumor suppressor gene product. EMBO J. 14: 503—511.
Parry, D.A., D. Mahony, K. Wills, and E. Lees. 1999. Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. Mol. Cell. Biol. 19: 1775—1783.
Peeper, D.S., T.M. Upton, M.H. Ladha, E. Neuman, J. Zalvide, R. Bernards, J.A. DeCaprio, and M.E. Ewen. 1997. Ras signaling linked to the cell-cycle machinery by the retinoblastoma protein. Nature 386: 177—181.
Pierce, G. B., Parchment, R. E., Lewellyn, A. L. 1991. Hydrogen peroxide as a mediator of programmed cell death in the blastocyst. Differentiation 46:181-186.
Polyak, K., J.-Y. Kato, M.J. Solomon, C.J. Sherr, J. Massague´ , J.M. Roberts, and A. Koff. 1994a. p27Kip1, a cyclin-cdk inhibitor, links transforming growth factor-b and contact inhibition to cell cycle arrest. Genes & Dev. 8: 9—22.
Russo, A.A., P.D. Jeffrey, A.K. Patten, J. Massague´ , and N.P. Pavletich. 1996. Crystal structure of the p27Kip1 cyclin-dependent kinase inhibitor bound to the cyclin A-cdk2 complex. Nature 382: 325—331.
Schulze-Osthoff, K., Bakker, A. C., Vanhaesebroeck, B., Beyaert, R., Jacob, W. A., Fiers, W. 1992. Cytototic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. J. Biol. Chem. 267:5317-5323.
Schulze-Osthoff, K., Beyaert, R., Vandevoorde, V., Haegeman, G., Fiers, W. 1993. Depletion of the mitochondrial electron transport abrogates the cytotoxic and gene-inductive effects of TNF. EMBO J. 12:3095-3104.
Schwaller, J., Koeffler, H. P., Niklaus, G., Loetscher, P., Nagel, S., Fey, M. F., Tobler, A. 1995. Posttrascriptional stabilization underlies p53-independent induction of p21WAF1/CIP1 in differentiating human leukemic cells. J. Clin. Invest. 95: 973-979.
Serrano, M., G.J. Hannon, and D. Beach. 1993. A new regulatory motif in cell cycle control causing specific inhibition of cyclinD/CDK4. Nature 366: 704—707.
Shaw, G., Kamen, R. 1986. A concserved AU sequence from the 3’ untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 46: 659-667.
Sherr, C.J. 1993. Mammalian G1 cyclins. Cell 73: 1059—1065.
Shiohara, M., El-Deiry, W. S., Wada, M., Nakamaki, T., Takeuchi, S., Yang, R., Chen, D. L., Vogelstein, B., Koeffler, H. P. 1994. Absence of WAF1 mutations in a variety of human malignancies. Blood. 8484:3781-3784.
Simon, H. U., Yousefi, S., Schranz, C., Schapowal, A., Bachert, C., Blaser, K. 1997. Direct demonstration of delayed eosinophil apoptosis as a mechanism causing tissue eosinophilia. J. Immunol. 158:3902-3908.
Smith, J. A. 1994. Neutrophils, host defense, and inflammation:A double-edged sword. J. Leukoc. Biol. 56:672-686.
Talley, A. K., Dewhurst, S., Perry, S. W. 1995. Tumor necrosis factor alpha-induced apoptosis in human neuronal cells:Protection by the antioxidant N-acetylcysteine and the genes Bcl-2 and crmA. Mol. Cell. Biol. 15:2359-2366.
Toyoshima, H. and T. Hunter. 1994. p27, a novel inhibitor of G1 cyclin/cdk protein kinase activity, is related to p21. Cell 78: 67—74.
Um, H. D., Orenstein, J. M., Wahl, S. M. 1996. Fas mediates apoptosis in human monocytes by a reactive oxygen intermediate dependent pathway. J. Immunol. 156:3469-3477.
Vachier, I., Chanez, P., Le Doucen, C., Dammon, M., Descomps, B., Godard, P. 1994. Enhancement of reactive oxygen species formation in stable and unstable asthmatic partients. Eur. Respir. J. 7:1585-1592.
Vives, E., Brodin, P., Lebleu, B. 1997. Atruncated HIV-1 TAT protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. J. Biol. Chem. 272: 16010-16017.
Wallach, D., Varfolomeev, E. E., Malinin, N. L., Goltsev, Y. V., Kovalenko, A. V., Boldin, M. P. 1999. Tumor necrosis factor receptor and Fas signaling mechanisms. Annu. Rev. Immunol. 17:331-367.
Warbrick, E., D.P. Lane, D.M. Glover, and L.S. Cox. 1995. A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21WAF1 and proliferating cell nuclear antigen. Curr. Biol.5: 275—282.
Watson, R. W., Rotstein, O. D., Jimenez, M., Parodo, J., Marshall, J. C. 1997. Augmented intracellular glutathione inhibits Fas-triggered apoptosis of activated human neutrophils. Blood. 89:4175-4181.
Weber, J.D., D.M. Raben, P.J. Phillips, and J.J. Baldassare. 1997. Sustained activation of extracellular-signal-regulated kinase 1 (ERK1) is required for the continued expression of cyclin D1 in G1 phase. Biochem. J. 326: 61—68.
Wedi, B., Straede, J., Wieland, B., Kapp, A. 1999. Eosinophil apoptosis is mediated by stimulators of cellular oxidative metabolisms and inhibited by antioxidants:Involvement of a yhiol-sensitive redox regulation in eosinophil cell death. Blood. 94:2365-2373.
Winston, J.T., S.R. Coats, Y.-Z. Wang, and W.J. Pledger. 1996. Regulation of the cell cycle machinery by oncogenic ras.Oncogene 12: 127—134.
Wong, G. H., Goeddel, D. V. 1989. Induction of manganous superoxide dismutase by tumor necrosis factor:Possible protective mechanism. Science. 242:941-943.
Xiong, Y., G.J. Hannon, H. Zhang, D. Casso, R. Kobayashi, and D. Beach. 1993a. p21 is a universal inhibitor of cyclin kinases. Nature 366: 701—704.
Xiong, Y., H. Zhang, and D. Beach. 1993b. Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation. Genes & Dev. 7: 1572—1583.
Yousefi, S., Green, D. R., Blaster, K., Simon, H. U. 1994. Protien-tyrosine phosphorylation regulates apoptosis in human eosinophils and neutrophils. Proc. Natl. Acdd. Sci. USA 91:10868-10872.
Zeng, Y. X., K.;El-Deiry, W. S. 1996. Regulation of p21WAF1/CIP1 expression by p53-independent pathways. Oncogene. 12: 1557-1564.
Zeng, Y. X., Somasundaram, K.;El-Deiry, W. S. 1997. AP2 inhibits cancer cell growth and activates p21WAF1/CIP1 expression. Nat. Genet. 15: 78-82.
Zhang, H., G.J. Hannon, and D. Beach. 1994. p21-containing cyclin kinases exist in both active and inactive states. Genes& Dev. 8: 1750—1758.

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