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Cell Growth and Development

E2F1 Induces Phosphorylation of p53 That Is Coincident with p53 Accumulation and Apoptosis

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Pages 5308-5318 | Received 29 Oct 2001, Accepted 26 Apr 2002, Published online: 27 Mar 2023

REFERENCES

  • Appella, E., and C. W. Anderson. 2001. Post-translational modifications and activation of p53 by genotoxic stresses. Eur. J. Biochem. 268: 2764–2772.
  • Ashcroft, M., M. H. Kubbutat, and K. H. Vousden. 1999. Regulation of p53 function and stability by phosphorylation. Mol. Cell. Biol. 19: 1751–1758.
  • Banin, S., L. Moyal, S. Shieh, Y. Taya, C. W. Anderson, L. Chessa, N. I. Smorodinsky, C. Prives, Y. Reiss, Y. Shiloh, and Y. Ziv. 1998. Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 281: 1674–1677.
  • Bates, S., A. C. Phillips, P. A. Clark, F. Stott, G. Peters, R. L. Ludwig, and K. H. Vousden. 1998. p14ARF links the tumour suppressors RB and p53. Nature 395: 124–125.
  • Blasina, A., B. D. Price, G. A. Turenne, and C. H. McGowan. 1999. Caffeine inhibits the checkpoint kinase ATM. Curr. Biol. 9: 1135–1138.
  • Blattner, C., A. Sparks, and D. Lane. 1999. Transcription factor E2F-1 is upregulated in response to DNA damage in a manner analogous to that of p53. Mol. Cell. Biol. 19: 3704–3713.
  • Canman, C. E., D. S. Lim, K. A. Cimprich, Y. Taya, K. Tamai, K. Sakaguchi, E. Appella, M. B. Kastan, and J. D. Siliciano. 1998. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science 281: 1677–1679.
  • Carnero, A., J. D. Hudson, C. M. Price, and D. H. Beach. 2000. p16INK4A and p19ARF act in overlapping pathways in cellular immortalization. Nat. Cell Biol. 2: 148–155.
  • Caspari, T. 2000. How to activate p53. Curr. Biol. 10: R315–R317.
  • Castillo, J. P., A. D. Yurochko, and T. F. Kowalik. 2000. Role of human cytomegalovirus immediate-early proteins in cell growth control. J. Virol. 74: 8028–8037.
  • Chehab, N. H., A. Malikzay, M. Appel, and T. D. Halazonetis. 2000. Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53. Genes Dev. 14: 278–288.
  • Chen, Q., F. C. Hung, L. Fromm, and P. A. Overbeek. 2000. Induction of cell cycle entry and cell death in postmitotic lens fiber cells by overexpression of E2F1 or E2F2. Investig. Ophthalmol. Vis. Sci. 41: 4223–4231.
  • Debbas, M., and E. White. 1993. Wild-type p53 mediates apoptosis by E1A, which is inhibited by E1B. Genes Dev. 7: 546–554.
  • DeGregori, J., T. Kowalik, and J. R. 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.
  • DeGregori, J., G. Leone, A. Miron, L. Jakoi, and J. R. Nevins. 1997. Distinct roles for E2F proteins in cell growth control and apoptosis. Proc. Natl. Acad. Sci. USA 94: 7245–7250.
  • de Stanchina, E., M. E. McCurrach, F. Zindy, S. Y. Shieh, G. Ferbeyre, A. V. Samuelson, C. Prives, M. F. Roussel, C. J. Sherr, and S. W. Lowe. 1998. E1A signaling to p53 involves the p19(ARF) tumor suppressor. Genes Dev. 12: 2434–2442.
  • Eilers, M., S. Schirm, and J. M. Bishop. 1991. The MYC protein activates transcription of the alpha-prothymosin gene. EMBO J. 10: 133–141.
  • 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 B. Vogelstein. 1993. WAF1, a potential mediator of p53 tumor suppression. Cell 75: 817–825.
  • Evan, G. I., A. H. Wyllie, C. S. Gilbert, T. D. Littlewood, H. Land, M. Brooks, C. M. Waters, L. Z. Penn, and D. C. Hancock. 1992. Induction of apoptosis in fibroblasts by c-myc protein. Cell 69: 119–128.
  • Eymin, B., L. Karayan, P. Seite, C. Brambilla, E. Brambilla, C. J. Larsen, and S. Gazzeri. 2001. Human ARF binds E2F1 and inhibits its transcriptional activity. Oncogene 20: 1033–1041.
  • Freedman, D. A., and A. J. Levine. 1998. Nuclear export is required for degradation of endogenous p53 by MDM2 and human papillomavirus E6. Mol. Cell. Biol. 18: 7288–7293.
  • Fuchs, S. Y., V. Adler, T. Buschmann, X. Wu, and Z. Ronai. 1998. Mdm2 association with p53 targets its ubiquitination. Oncogene 17: 2543–2547.
  • Giaccia, A. J., and M. B. Kastan. 1998. The complexity of p53 modulation: emerging patterns from divergent signals. Genes Dev. 12: 2973–2983.
  • Harbour, J. W., and D. C. Dean. 2000. The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev. 14: 2393–2409.
  • 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.
  • Haupt, Y., R. Maya, A. Kazaz, and M. Oren. 1997. Mdm2 promotes the rapid degradation of p53. Nature 387: 296–299.
  • Hermeking, H., and D. Eick. 1994. Mediation of c-Myc-induced apoptosis by p53. Science 265: 2091–2093.
  • Hiebert, S. W., G. Packham, D. K. Strom, R. Haffner, M. Oren, G. Zambetti, and J. L. Cleveland. 1995. E2F-1:DP-1 induces p53 and overrides survival factors to trigger apoptosis. Mol. Cell. Biol. 15: 6864–6874.
  • Hirao, A., Y. Y. Kong, S. Matsuoka, A. Wakeham, J. Ruland, H. Yoshida, D. Liu, S. J. Elledge, and T. W. Mak. 2000. DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science 287: 1824–1827.
  • Hofferer, M., C. Wirbelauer, B. Humar, and W. Krek. 1999. Increased levels of E2F-1-dependent DNA binding activity after UV- or gamma-irradiation. Nucleic Acids Res. 27: 491–495.
  • Honda, R., H. Tanaka, and H. Yasuda. 1997. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 420: 25–27.
  • Inoue, K., M. F. Roussel, and C. J. Sherr. 1999. Induction of ARF tumor suppressor gene expression and cell cycle arrest by transcription factor DMP1. Proc. Natl. Acad. Sci. USA 96: 3993–3998.
  • Irwin, M., M. C. Marin, A. C. Phillips, R. S. Seelan, D. I. Smith, W. Liu, E. R. Flores, K. Y. Tsai, T. Jacks, K. H. Vousden, and W. G. Kaelin, Jr. 2000. Role for the p53 homologue p73 in E2F-1-induced apoptosis. Nature 407: 645–648.
  • Ivey-Hoyle, M., R. Conroy, H. E. Huber, P. J. Goodhart, A. Oliff, and D. C. Heimbrook. 1993. Cloning and characterization of E2F-2, a novel protein with the biochemical properties of transcription factor E2F. Mol. Cell. Biol. 13: 7802–7812.
  • Johnson, D. G., J. K. Schwarz, W. D. Cress, and J. R. Nevins. 1993. Expression of transcription factor E2F1 induces quiescent cells to enter S phase. Nature 365: 349–352.
  • Jones, S. N., A. T. Sands, A. R. Hancock, H. Vogel, L. A. Donehower, S. P. Linke, G. M. Wahl, and A. Bradley. 1996. The tumorigenic potential and cell growth characteristics of p53-deficient cells are equivalent in the presence or absence of Mdm2. Proc. Natl. Acad. Sci. USA 93: 14106–14111.
  • Kamijo, T., F. Zindy, M. F. Roussel, D. E. Quelle, J. R. Downing, R. A. Ashmun, G. Grosveld, and C. J. Sherr. 1997. Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell 91: 649–659.
  • Kastan, M. B., O. Onyekwere, D. Sidransky, B. Vogelstein, and R. W. Craig. 1991. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 51: 6304–6311.
  • Kowalik, T. F., J. DeGregori, G. Leone, L. Jakoi, and J. R. Nevins. 1998. E2F1-specific induction of apoptosis and p53 accumulation, which is blocked by Mdm2. Cell Growth Differ. 9: 113–118.
  • Kowalik, T. F., J. DeGregori, J. K. Schwarz, and J. R. Nevins. 1995. E2F1 overexpression in quiescent fibroblasts leads to induction of cellular DNA synthesis and apoptosis. J. Virol. 69: 2491–2500.
  • Lakin, N. D., B. C. Hann, and S. P. Jackson. 1999. The ataxia-telangiectasia related protein ATR mediates DNA-dependent phosphorylation of p53. Oncogene 18: 3989–3995.
  • Lees, J. A., M. Saito, M. Vidal, M. Valentine, T. Look, E. Harlow, N. Dyson, and K. Helin. 1993. The retinoblastoma protein binds to a family of E2F transcription factors. Mol. Cell. Biol. 13: 7813–7825.
  • Lin, W. C., F. T. Lin, and J. R. Nevins. 2001. Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation. Genes Dev. 15: 1833–1844.
  • Lissy, N. A., P. K. Davis, M. Irwin, W. G. Kaelin, and S. F. Dowdy. 2000. A common E2F-1 and p73 pathway mediates cell death induced by TCR activation. Nature 407: 642–645.
  • Liu, Q., S. Guntuku, X. S. Cui, S. Matsuoka, D. Cortez, K. Tamai, G. Luo, S. Carattini-Rivera, F. DeMayo, A. Bradley, L. A. Donehower, and S. J. Elledge. 2000. Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev. 14: 1448–1459.
  • Macleod, K. F., Y. Hu, and T. Jacks. 1996. Loss of Rb activates both p53-dependent and independent cell death pathways in the developing mouse nervous system. EMBO J. 15: 6178–6188.
  • Martelli, F., T. Hamilton, D. P. Silver, N. E. Sharpless, N. Bardeesy, M. Rokas, R. A. DePinho, D. M. Livingston, and S. R. Grossman. 2001. p19ARF targets certain E2F species for degradation Proc. Natl. Acad. Sci. USA 98: 4455–4460.
  • Matsuoka, S., G. Rotman, A. Ogawa, Y. Shiloh, K. Tamai, and S. J. Elledge. 2000. Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro. Proc. Natl. Acad. Sci. USA 97: 10389–10394.
  • McMasters, K. M., R. Montes de Oca Luna, J. R. Pena, and G. Lozano. 1996. mdm2 deletion does not alter growth characteristics of p53-deficient embryo fibroblasts. Oncogene 13: 1731–1736.
  • Morgenbesser, S. D., B. O. Williams, T. Jacks, and R. A. DePinho. 1994. p53-dependent apoptosis produced by Rb-deficiency in the developing mouse lens. Nature 371: 72–74.
  • Muller, H., A. P. Bracken, R. Vernell, M. C. Moroni, F. Christians, E. Grassilli, E. Prosperini, E. Vigo, J. D. Oliner, and K. Helin. 2001. E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis. Genes Dev. 15: 267–285.
  • Nevins, J. R. 1992. E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. Science 258: 424–429.
  • Nevins, J. R. 1998. Toward an understanding of the functional complexity of the E2F and retinoblastoma families. Cell Growth Differ. 9: 585–593.
  • Nevins, J. R., J. DeGregori, L. Jakoi, and G. Leone. 1997. Functional analysis of E2F transcription factor. Methods Enzymol. 283: 205–219.
  • Nip, J., D. K. Strom, C. M. Eischen, J. L. Cleveland, G. P. Zambetti, and S. W. Hiebert. 2001. E2F-1 induces the stabilization of p53 but blocks p53-mediated transactivation. Oncogene 20: 910–920.
  • Pan, H., C. Yin, N. J. Dyson, E. Harlow, L. Yamasaki, and T. Van Dyke. 1998. Key roles for E2F1 in signaling p53-dependent apoptosis and in cell division within developing tumors. Mol. Cell 2: 283–292.
  • Pierce, A. M., I. B. Gimenez-Conti, R. Schneider-Broussard, L. A. Martinez, C. J. Conti, and D. G. Johnson. 1998. Increased E2F1 activity induces skin tumors in mice heterozygous and nullizygous for p53. Proc. Natl. Acad. Sci. USA 95: 8858–8863.
  • 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 R. A. DePinho. 1998. The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53. Cell 92: 713–723.
  • Qin, X. Q., D. M. Livingston, W. G. Kaelin, Jr., and P. D. Adams. 1994. Deregulated transcription factor E2F-1 expression leads to S-phase entry and p53-mediated apoptosis. Proc. Natl. Acad. Sci. USA 91: 10918–10922.
  • Robertson, K. D., and P. A. 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.
  • Russell, J. L., J. T. Powers, R. J. Rounbehler, P. M. Rogers, C. J. Conti, and D. G. Johnson. 2002. ARF differentially modulates apoptosis induced by E2F1 and Myc. Mol. Cell. Biol. 22: 1360–1368.
  • Sarkaria, J. N., E. C. Busby, R. S. Tibbetts, P. Roos, Y. Taya, L. M. Karnitz, and R. T. Abraham. 1999. Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. Cancer Res. 59: 4375–4382.
  • Schwarz, J. K., C. H. Bassing, I. Kovesdi, M. B. Datto, M. Blazing, S. George, X. F. Wang, and J. R. Nevins. 1995. Expression of the E2F1 transcription factor overcomes type beta transforming growth factor-mediated growth suppression. Proc. Natl. Acad. Sci. USA 92: 483–487.
  • Sears, R., K. Ohtani, and J. R. Nevins. 1997. Identification of positively and negatively acting elements regulating expression of the E2F2 gene in response to cell growth signals. Mol. Cell. Biol. 17: 5227–5235.
  • Serrano, M., H. Lee, L. Chin, C. Cordon-Cardo, D. Beach, and R. A. DePinho. 1996. Role of the INK4a locus in tumor suppression and cell mortality. Cell 85: 27–37.
  • Shieh, S. Y., J. Ahn, K. Tamai, Y. Taya, and C. Prives. 2000. The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev. 14: 289–300.
  • Stiewe, T., and B. M. Putzer. 2000. Role of the p53-homologue p73 in E2F1-induced apoptosis. Nat. Genet. 26: 464–469.
  • Tolbert, D., X. Lu, C. Yin, M. Tantama, and T. Van Dyke. 2002. p19(ARF) is dispensable for oncogenic stress-induced p53-mediated apoptosis and tumor suppression in vivo. Mol. Cell. Biol. 22: 370–377.
  • Tsai, K. Y., Y. Hu, K. F. Macleod, D. Crowley, L. Yamasaki, and T. Jacks. 1998. Mutation of E2f-1 suppresses apoptosis and inappropriate S phase entry and extends survival of Rb-deficient mouse embryos. Mol. Cell 2: 293–304.
  • Tsai, K. Y., D. MacPherson, D. A. Rubinson, D. Crowley, and T. Jacks. 2002. ARF is not required for apoptosis in Rb mutant mouse embryos. Curr. Biol. 12: 159–163.
  • Unger, T., R. V. Sionov, E. Moallem, C. L. Yee, P. M. Howley, M. Oren, and Y. Haupt. 1999. Mutations in serines 15 and 20 of human p53 impair its apoptotic activity. Oncogene 18: 3205–3212.
  • Vigo, E., H. Muller, E. Prosperini, G. Hateboer, P. Cartwright, M. C. Moroni, and K. Helin. 1999. CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S phase. Mol. Cell. Biol. 19: 6379–6395.
  • Vousden, K. H. 2000. p53: death star. Cell 103: 691–694.
  • Wu, X., and A. J. Levine. 1994. p53 and E2F-1 cooperate to mediate apoptosis. Proc. Natl. Acad. Sci. USA 91: 3602–3606.
  • Wu, Z., J. Earle, S. Saito, C. W. Anderson, E. Appella, and Y. Xu. 2002. Mutation of mouse p53 Ser23 and the response to DNA damage. Mol. Cell. Biol. 22: 2441–2449.
  • Xiong, Y., G. J. Hannon, H. Zhang, D. Casso, R. Kobayashi, and D. Beach. 1993. p21 is a universal inhibitor of cyclin kinases. Nature 366: 701–704.
  • Zhang, Y., Y. Xiong, and W. G. 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.
  • Zhou, B. B., and S. J. Elledge. 2000. The DNA damage response: putting checkpoints in perspective. Nature 408: 433–439.
  • Ziebold, U., T. Reza, A. Caron, and J. A. Lees. 2001. E2F3 contributes both to the inappropriate proliferation and to the apoptosis arising in Rb mutant embryos. Genes Dev. 15: 386–391.
  • Zindy, F., C. M. Eischen, D. H. Randle, T. Kamijo, J. L. Cleveland, C. J. Sherr, and M. F. Roussel. 1998. Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization. Genes Dev. 12: 2424–2433.

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