Uncoupling between Phenotypic Senescence and Cell Cycle Arrest in Aging p21-Deficient Fibroblasts

REFERENCES

• Alcorta, D. A., Xiong, Y., Phelps, D., Hannon, G., Beach, D., and Barrett, J. C.. 1996. Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proc. Natl. Acad. Sci. USA 93:13742–13747
   PubMed Web of Science ®Google Scholar
• Atadja, P., Wong, H., Garkavtsev, I., Veillette, C., and Riabowol, K.. 1995. Increased activity of p53 in senescing fibroblasts. Proc. Natl. Acad. Sci. USA 92:8348–8352
   PubMed Web of Science ®Google Scholar
• Beijersbergen, R. L., Carlee, L., Kerkhoven, R. M., and Bernards, R.. 1995. Regulation of the retinoblastoma protein-related p107 by G1 cyclin complexes. Genes Dev. 9:1340–1353
   PubMedGoogle Scholar
• Bond, J. A., Haughton, M. F., Rowson, J. M., Smith, P. J., Gire, V., Wynford-Thomas, D., and Wyllie, F. S.. 1999. Control of replicative life span in human cells: barriers to clonal expansion intermediate between M1 senescence and M2 crisis. Mol. Cell. Biol. 19:3103–3114
   PubMedGoogle Scholar
• Bond, J. A., Wyllie, F. S., and Wynford, T. D.. 1994. Escape from senescence in human diploid fibroblasts induced directly by mutant p53. Oncogene 9:1885–1889
   PubMedGoogle Scholar
• Bresnahan, W. A., Boldogh, I., Ma, T., Albrecht, T., and Thompson, E. A.. 1996. Cyclin E/Cdk2 activity is controlled by different mechanisms in the G0 and G1 phases of the cell cycle. Cell Growth Differ. 7:1283–1290
   PubMedGoogle Scholar
• Brown, J. P., Wei, W., and Sedivy, J. M.. 1997. Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts. Science 277:831–834
   PubMed Web of Science ®Google Scholar
• Brugarolas, J., Chandrasekaran, C., Gordon, J. I., Beach, D., Jacks, T., and Hannon, G. J.. 1995. Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature 377:552–557
   PubMed Web of Science ®Google Scholar
• Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J. P., Sedivy, J. M., Kinzler, K. W., and Vogelstein, B.. 1998. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 282:1497–1501
   PubMed Web of Science ®Google Scholar
• Burkhart, B. A., Alcorta, D. A., Chiao, C., Isaacs, J. S., and Barrett, J. C.. 1999. Two posttranscriptional pathways that regulate p21(Cip1/Waf1/Sdi1) are identified by HPV16-E6 interaction and correlate with life span and cellular senescence. Exp. Cell. Res. 247:168–175
   PubMedGoogle Scholar
• Campisi, J.. 1997. The biology of replicative senescence. Eur. J. Cancer 33:703–709
   PubMed Web of Science ®Google Scholar
• Carnero, A., Hudson, J. D., Price, C. M., and Beach, D. H.. 2000. p16INK4A and p19ARF act in overlapping pathways in cellular immortalization. Nat. Cell Biol. 2:148–155
   PubMed Web of Science ®Google Scholar
• Carrano, A. C., Eytan, E., Hershko, A., and Pagano, M.. 1999. SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Nat. Cell Biol. 1:193–199
   PubMed Web of Science ®Google Scholar
• Cheng, M., Olivier, P., Diehl, J. A., Fero, M., Roussel, M. F., Roberts, J. M., and Sherr, C. J.. 1999. The p21(Cip1) and p27(Kip1) CDK ‘inhibitors’ are essential activators of cyclin D-dependent kinases in murine fibroblasts. EMBO J. 18:1571–1583
   PubMed Web of Science ®Google Scholar
• Dimri, G. P., Itahana, K., Acosta, M., and Campisi, J.. 2000. Regulation of a senescence checkpoint response by the E2F1 transcription factor and p14(ARF) tumor suppressor. Mol. Cell. Biol. 20:273–285
   PubMed Web of Science ®Google Scholar
• Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., Pereira-Smith, O. et al. 1995. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl. Acad. Sci. USA 92:9363–9367
   PubMed Web of Science ®Google Scholar
• Dulić, V., Drullinger, L. F., Lees, E., Reed, S. I., and Stein, G. H.. 1993. Altered regulation of G1 cyclins in senescent human diploid fibroblasts: accumulation of inactive cyclin E-Cdk2 and cyclin D1-Cdk2 complexes. Proc. Natl. Acad. Sci. USA 90:11034–11038
   PubMed Web of Science ®Google Scholar
• Dulić, V., Kaufmann, W. K., Wilson, S. J., Tlsty, T. D., Lees, E., Harper, J. W., Elledge, S. J., and Reed, S. I.. 1994. p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest. Cell 76:1013–1023
   PubMed Web of Science ®Google Scholar
• Dulić, V., Stein, G. H., Far, D. F., and Reed, S. I.. 1998. Nuclear accumulation of p21Cip1 at the onset of mitosis: a role at the G2/M-phase transition. Mol. Cell. Biol. 18:546–557
   PubMed Web of Science ®Google Scholar
• Ezhevsky, S. A., Nagahara, H., Vocero, A. A., Gius, D. R., Wei, M. C., and Dowdy, S. F.. 1997. Hypo-phosphorylation of the retinoblastoma protein (pRb) by cyclin D:Cdk4/6 complexes results in active pRb. Proc. Natl. Acad. Sci. USA 94:10699–10704
   PubMed Web of Science ®Google Scholar
• Filatov, L., Golubovskaya, V., Hurt, J. C., Byrd, L. L., Phillips, J. M., and Kaufmann, W. K.. 1998. Chromosomal instability is correlated with telomere erosion and inactivation of G2 checkpoint function in human fibroblasts expressing human papillomavirus type 16 E6 oncoprotein. Oncogene 16:1825–1838
   PubMedGoogle Scholar
• Gao, Q., Srinivasan, S., Boyer, S. N., Wazer, D. E., and Band, V.. 1999. The E6 oncoproteins of high-risk papillomaviruses bind to a novel putative GAP protein, E6TP1, and target it for degradation. Mol. Cell. Biol. 19:733–744
   PubMed Web of Science ®Google Scholar
• Grana, X., Garriga, J., and Mayol, X.. 1998. Role of the retinoblastoma protein family, pRb, p107, and p130 in the negative control of cell growth. Oncogene 17:3365–3383
   PubMed Web of Science ®Google Scholar
• Hara, E., Smith, R., Parry, D., Tahara, H., Stone, S., and Peters, G.. 1996. Regulation of p16CDKN2 expression and its implications for cell immortalization and senescence. Mol. Cell. Biol. 16:859–867
   PubMed Web of Science ®Google Scholar
• Harbour, J. W., Luo, R. X., Dei Santi, A., Postigo, A. A., and Dean, D. C.. 1999. Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. Cell 98:859–869
   PubMed Web of Science ®Google Scholar
• Hayflick, L.. 1965. The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res. 37:614–636
   PubMed Web of Science ®Google Scholar
• Hengst, L., Gopfert, U., Lashuel, H. A., and Reed, S. I.. 1998. Complete inhibition of Cdk/cyclin by one molecule of p21(Cip1). Genes Dev. 12:3882–3888
   PubMedGoogle Scholar
• Kaelin, W. G.Jr.. 1999. Functions of the retinoblastoma protein. Bioessays 21:950–958
   PubMed Web of Science ®Google Scholar
• Kamijo, T., Zindy, F., Roussel, M. F., Quelle, D. E., Downing, J. R., Ashmun, R. A., Grosveld, G., and Sherr, C. J.. 1997. Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell 91:649–659
   PubMed Web of Science ®Google Scholar
• Kitagawa, M., Higashi, H., Jung, H. K., Suzuki-Takahashi, I., Ikeda, M., Tamai, K., Kato, J., Segawa, K., Yoshida, E., Nishimura, S., and Taya, Y.. 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
   PubMed Web of Science ®Google Scholar
• Kulju, K. S., and Lehman, J. M.. 1995. Increased p53 protein associated with aging in human diploid fibroblasts. Exp. Cell Res. 217:336–345
   PubMedGoogle Scholar
• LaBaer, J., Garrett, M. D., Stevenson, L. F., Slingerland, J. M., Sandhu, C., Chou, H. S., Fattaey, A., and Harlow, E.. 1997. New functional activities for the p21 family of CDK inhibitors. Genes Dev. 11:847–862
   PubMed Web of Science ®Google Scholar
• Lloyd, A. C.. 2000. p53: only ARF the story. Nat. Cell Biol. 2:48–50
   PubMedGoogle Scholar
• Lukas, J., Herzinger, T., Hansen, K., Moroni, M. C., Resnitzky, D., Helin, K., Reed, S. I., and Bartek, J.. 1997. Cyclin E-induced S phase without activation of the pRb/E2F pathway. Genes Dev. 11:1479–1492
   PubMed Web of Science ®Google Scholar
• Lukas, J., Sorensen, C. S., Lukas, C., Santoni-Rugiu, E., and Bartek, J.. 1999. p16INK4a, but not constitutively active pRb, can impose a sustained G1 arrest: molecular mechanisms and implications for oncogenesis. Oncogene 18:3930–3935
   PubMedGoogle Scholar
• Lundberg, A. S., and Weinberg, R. A.. 1998. Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. Mol. Cell. Biol. 18:753–761
   PubMed Web of Science ®Google Scholar
• McConnell, B. B., Starborg, M., Brookes, S., and Peters, G.. 1998. Inhibitors of cyclin-dependent kinases induce features of replicative senescence in early passage human diploid fibroblasts. Curr. Biol. 8:351–354
   PubMed Web of Science ®Google Scholar
• Medcalf, A. S., Klein-Szanto, A. J., and Cristofalo, V. J.. 1996. Expression of p21 is not required for senescence of human fibroblasts. Cancer Res. 56:4582–4585
   PubMedGoogle Scholar
• Meyyappan, M., Wong, H., Hull, C., and Riabowol, K. T.. 1998. Increased expression of cyclin D2 during multiple states of growth arrest in primary and established cells. Mol. Cell. Biol. 18:3163–3172
   PubMedGoogle Scholar
• Millis, A. J., Hoyle, M., McCue, H. M., and Martini, H.. 1992. Differential expression of metalloproteinase and tissue inhibitor of metalloproteinase genes in aged human fibroblasts. Exp. Cell. Res. 201:373–379
   PubMed Web of Science ®Google Scholar
• Mitra, J., Dai, C. Y., Somasundaram, K., El-Deiry, W. S., Satyamoorthy, K., Herlyn, M., and Enders, G. H.. 1999. Induction of p21(WAF1/CIP1) and inhibition of Cdk2 mediated by the tumor suppressor p16(INK4a). Mol. Cell. Biol. 19:3916–3928
   PubMed Web of Science ®Google Scholar
• Noda, A., Ning, Y., Venable, S. F., Pereira, S. O., and Smith, J. R.. 1994. Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp. Cell Res. 211:90–98
   PubMed Web of Science ®Google Scholar
• Ohtsubo, M., Theodoras, A. M., Schumacher, J., Roberts, J. M., and Pagano, M.. 1995. Human cyclin E, a nuclear protein essential for the G1-to-S phase transition. Mol. Cell. Biol. 15:2612–2624
   PubMed Web of Science ®Google Scholar
• Palmero, I., McConnell, B., Parry, D., Brookes, S., Hara, E., Bates, S., Jat, P., and Peters, G.. 1997. Accumulation of p16INK4a in mouse fibroblasts as a function of replicative senescence and not of retinoblastoma gene status. Oncogene 15:495–503
   PubMedGoogle Scholar
• Pantoja, C., and Serrano, M.. 1999. Murine fibroblasts lacking p21 undergo senescence and are resistant to transformation by oncogenic Ras. Oncogene 18:4974–4982
   PubMed Web of Science ®Google Scholar
• Planas-Silva, M. D., and Weinberg, R. A.. 1997. Estrogen-dependent cyclin E-cdk2 activation through p21 redistribution. Mol. Cell. Biol. 17:4059–4069
   PubMed Web of Science ®Google Scholar
• Ponzio, G., Loubat, A., Rochet, N., Turchi, L., Rezzonico, R., Farahi Far, D., Dulić, V., and Rossi, B.. 1998. Early G1 growth arrest of hybridoma B cells by DMSO involves cyclin D2 inhibition and p21[CIP1] induction. Oncogene 17:1159–1166
   PubMedGoogle Scholar
• Resnitzky, D., and Reed, S. I.. 1995. Different roles for cyclins D1 and E in regulation of the G1-to-S transition. Mol. Cell. Biol. 15:3463–3469
   PubMed Web of Science ®Google Scholar
• Rogan, E. M., Bryan, T. M., Hukku, B., Maclean, K., Chang, A. C., Moy, E. L., Englezou, A., Warneford, S. G., Dalla-Pozza, L., and Reddel, R. R.. 1995. Alterations in p53 and p16INK4 expression and telomere length during spontaneous immortalization of Li-Fraumeni syndrome fibroblasts. Mol. Cell. Biol. 15:4745–4753
   PubMed Web of Science ®Google Scholar
• Rubin, E., Tamrakar, S., and Ludlow, J. W.. 1998. Protein phosphatase type 1, the product of the retinoblastoma susceptibility gene, and cell cycle control. Front. Biosci. 3:D1209–D1219
   PubMedGoogle Scholar
• Serrano, M., Lee, H., Chin, L., Cordon-Cardo, C., Beach, D., and DePinho, R. A.. 1996. Role of the INK4a locus in tumor suppression and cell mortality. Cell 85:27–37
   PubMed Web of Science ®Google Scholar
• Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., and Lowe, S. W.. 1997. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88:593–602
   PubMed Web of Science ®Google Scholar
• Shay, J. W., Pereira, S. O., and Wright, W. E.. 1991. A role for both RB and p53 in the regulation of human cellular senescence. Exp. Cell Res. 196:33–39
   PubMed Web of Science ®Google Scholar
• Shay, J. W., Van der Haegen, B., Ying, Y., and Wright, W. E.. 1993. The frequency of immortalization of human fibroblasts and mammary epithelial cells transfected with SV40 large T-antigen. Exp. Cell Res. 209:45–52
   PubMed Web of Science ®Google Scholar
• Shay, J. W., Wright, W. E., Brasiskyte, D., and van der Haegen, B.. 1993. E6 of human papillomavirus type 16 can overcome the M1 stage of immortalization in human mammary epithelial cells but not in human fibroblasts. Oncogene 8:1407–1413
   PubMed Web of Science ®Google Scholar
• Shelton, D. N., Chang, E., Whittier, P. S., Choi, D., and Funk, W. D.. 1999. Microarray analysis of replicative senescence. Curr. Biol. 9:939–945
   PubMed Web of Science ®Google Scholar
• Sherr, C. J., and Roberts, J. M.. 1999. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 13:1501–1512
   PubMed Web of Science ®Google Scholar
• Spruck, C. H., Won, K. A., and Reed, S. I.. 1999. Deregulated cyclin E induces chromosome instability. Nature 401:297–300
   PubMed Web of Science ®Google Scholar
• Stein, G. H., Beeson, M., and Gordon, L.. 1990. Failure to phosphorylate the retinoblastoma gene product in senescent human fibroblasts. Science 249:666–669
   PubMed Web of Science ®Google Scholar
• Stein, G. H., Drullinger, L. F., Soulard, A., and Dulić, V.. 1999. Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. Mol. Cell. Biol. 19:2109–2117
   PubMed Web of Science ®Google Scholar
• Stein, G. H., and Dulić, V.. 1995. Origins of G1 arrest in senescent human fibroblasts. Bioessays 17:537–543
   PubMedGoogle Scholar
• Sutterluty, H., Chatelain, E., Marti, A., Wirbelauer, C., Senften, M., Muller, U., and Krek, W.. 1999. p45SKP2 promotes p27Kip1 degradation and induces S phase in quiescent cells. Nat. Cell Biol. 1:207–214
   PubMed Web of Science ®Google Scholar
• Thomas, M., and Banks, L.. 1999. Human papillomavirus (HPV) E6 interactions with Bak are conserved amongst E6 proteins from high and low risk HPV types. J. Gen. Virol. 80:1513–1517
   PubMed Web of Science ®Google Scholar
• Tong, X., Salgia, R., Li, J. L., Griffin, J. D., and Howley, P. M.. 1997. The bovine papillomavirus E6 protein binds to the LD motif repeats of paxillin and blocks its interaction with vinculin and the focal adhesion kinase. J. Biol. Chem. 272:33373–33376
   PubMedGoogle Scholar
• Wei, W., and Sedivy, J. M.. 1999. Differentiation between senescence (M1) and crisis (M2) in human fibroblast cultures. Exp. Cell Res. 253:519–522
   PubMedGoogle Scholar
• Xiao, Z. X., Ginsberg, D., Ewen, M., and Livingston, D. M.. 1996. Regulation of the retinoblastoma protein-related protein p107 by G1 cyclin-associated kinases. Proc. Natl. Acad. Sci. USA 93:4633–4637
   PubMedGoogle Scholar
• Xiong, Y., Kuppuswamy, D., Li, Y., Livanos, E. M., Hixon, M., White, A., Beach, D., and Tlsty, T. D.. 1996. Alteration of cell cycle kinase complexes in human papillomavirus E6- and E7-expressing fibroblasts precedes neoplastic transformation. J. Virol. 70:999–1008
   PubMed Web of Science ®Google Scholar
• Yu, Z. K., Gervais, J. L., and Zhang, H.. 1998. Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21(CIP1/WAF1) and cyclin D proteins. Proc. Natl. Acad. Sci. USA 95:11324–11329
   PubMed Web of Science ®Google Scholar
• Zhang, H., Kobayashi, R., Galaktionov, K., and Beach, D.. 1995. p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase. Cell 82:915–925
   PubMed Web of Science ®Google Scholar
• Zhu, J., Woods, D., McMahon, M., and Bishop, J. M.. 1998. Senescence of human fibroblasts induced by oncogenic Raf. Genes Dev. 12:2997–3007
   PubMed Web of Science ®Google Scholar
• Zimmermann, H., Degenkolbe, R., Bernard, H. U., and O'Connor, M. J.. 1999. The human papillomavirus type 16 E6 oncoprotein can down-regulate p53 activity by targeting the transcriptional coactivator CBP/p300. J. Virol. 73:6209–6219
   PubMed Web of Science ®Google Scholar
• Zindy, F., Quelle, D. E., Roussel, M. F., and Sherr, C. J.. 1997. Expression of the p16INK4a tumor suppressor versus other INK4 family members during mouse development and aging. Oncogene 15:203–211
   PubMedGoogle Scholar