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Cell Growth and Development

Retinoblastoma Tumor Suppressor: Analyses of Dynamic Behavior in Living Cells Reveal Multiple Modes of Regulation

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Pages 8172-8188 | Received 29 May 2003, Accepted 06 Aug 2003, Published online: 27 Mar 2023

REFERENCES

  • Alcalay, M., L. Tomassoni, E. Colombo, S. Stoldt, F. Grignani, M. Fagioli, L. Szekely, K. Helin, and P. G. Pelicci. 1998. The promyelocytic leukemia gene product (PML) forms stable complexes with the retinoblastoma protein. Mol. Cell. Biol. 18: 1084–1093.
  • Angus, S. P., A. F. Fribourg, M. P. Markey, S. L. Williams, H. F. Horn, J. DeGregori, T. F. Kowalik, K. Fukasawa, and E. S. Knudsen. 2002. Active RB elicits late G1/S inhibition. Exp. Cell Res. 276: 201–213.
  • Angus, S. P., L. J. Wheeler, S. A. Ranmal, X. Zhang, M. P. Markey, C. K. Mathews, and E. S. Knudsen. 2002. Retinoblastoma tumor suppressor targets dNTP metabolism to regulate DNA replication. J. Biol. Chem. 277: 44376–44384.
  • Chew, Y. P., M. Ellis, S. Wilkie, and S. Mittnacht. 1998. pRB phosphorylation mutants reveal role of pRB in regulating S phase completion by a mechanism independent of E2F. Oncogene 17: 2177–2186.
  • Dahiya, A., S. Wong, S. Gonzalo, M. Gavin, and D. C. Dean. 2001. Linking the Rb and polycomb pathways. Mol. Cell 8: 557–569.
  • DeGregori, J. 2002. The genetics of the E2F family of transcription factors: shared functions and unique roles. Biochim. Biophys. Acta 1602: 131–150.
  • Dimitrova, D. S., and R. Berezney. 2002. The spatio-temporal organization of DNA replication sites is identical in primary, immortalized and transformed mammalian cells. J. Cell Sci. 115: 4037–4051.
  • Dunaief, J. L., B. E. Strober, S. Guha, P. A. Khavari, K. Alin, J. Luban, M. Begemann, G. R. Crabtree, and S. P. Goff. 1994. The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest. Cell 79: 119–130.
  • Durfee, T., M. A. Mancini, D. Jones, S. J. Elledge, and W. H. Lee. 1994. The amino-terminal region of the retinoblastoma gene product binds a novel nuclear matrix protein that co-localizes to centers for RNA processing. J. Cell Biol. 127: 609–622.
  • Fry, C. J., and C. L. Peterson. 2001. Chromatin remodeling enzymes: who's on first? Curr. Biol. 11: R185–R197.
  • Giangrande, P. H., T. C. Hallstrom, C. Tunyaplin, K. Calame, and J. R. Nevins. 2003. Identification of E-box factor TFE3 as a functional partner for the E2F3 transcription factor. Mol. Cell. Biol. 23: 3707–3720.
  • Goodman, R. H., and S. Smolik. 2000. CBP/p300 in cell growth, transformation, and development. Genes Dev. 14: 1553–1577.
  • Hannan, K. M., B. K. Kennedy, A. H. Cavanaugh, R. D. Hannan, I. Hirschler-Laszkiewicz, L. S. Jefferson, and L. I. Rothblum. 2000. RNA polymerase I transcription in confluent cells: Rb downregulates rDNA transcription during confluence-induced cell cycle arrest. Oncogene 19: 3487–3497.
  • Harbour, J. W., and D. C. Dean. 2000. Chromatin remodeling and Rb activity. Curr. Opin. Cell Biol. 12: 685–689.
  • Harbour, J. W., and D. C. Dean. 2001. Corepressors and retinoblastoma protein function. Curr. Top. Microbiol. Immunol. 254: 137–144.
  • Harbour, J. W., and D. C. Dean. 2000. The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev. 14: 2393–2409.
  • Hinds, P. W., S. Mittnacht, V. Dulic, A. Arnold, S. I. Reed, and R. A. Weinberg. 1992. Regulation of retinoblastoma protein functions by ectopic expression of human cyclins. Cell 70: 993–1006.
  • Kaelin, W. G., Jr. 1997. Alterations in G1/S cell-cycle control contributing to carcinogenesis. Ann. N. Y. Acad. Sci. 833: 29–33.
  • Kennedy, B. K., D. A. Barbie, M. Classon, N. Dyson, and E. Harlow. 2000. Nuclear organization of DNA replication in primary mammalian cells. Genes Dev. 14: 2855–2868.
  • Khavari, P. A., C. L. Peterson, J. W. Tamkun, D. B. Mendel, and G. R. Crabtree. 1993. BRG1 contains a conserved domain of the SWI2/SNF2 family necessary for normal mitotic growth and transcription. Nature 366: 170–174.
  • Kimura, H., and P. R. Cook. 2001. Kinetics of core histones in living human cells: little exchange of H3 and H4 and some rapid exchange of H2B. J. Cell Biol. 153: 1341–1353.
  • Kingston, R. E., and G. J. Narlikar. 1999. ATP-dependent remodeling and acetylation as regulators of chromatin fluidity. Genes Dev. 13: 2339–2352.
  • Knudsen, E. S., C. Buckmaster, T. T. Chen, J. R. Feramisco, and J. Y. Wang. 1998. Inhibition of DNA synthesis by RB: effects on G1/S transition and S-phase progression. Genes Dev. 12: 2278–2292.
  • Knudsen, E. S., and J. Y. Wang. 1996. Differential regulation of retinoblastoma protein function by specific Cdk phosphorylation sites. J. Biol. Chem. 271: 8313–8320.
  • Knudsen, E. S., and J. Y. Wang. 1997. Dual mechanisms for the inhibition of E2F binding to RB by cyclin-dependent kinase-mediated RB phosphorylation. Mol. Cell. Biol. 17: 5771–5783.
  • Knudsen, K. E., A. F. Fribourg, M. W. Strobeck, J. M. Blanchard, and E. S. Knudsen. 1999. Cyclin A is a functional target of retinoblastoma tumor suppressor protein-mediated cell cycle arrest. J. Biol. Chem. 274: 27632–27641.
  • Lee, W. H., J. Y. Shew, F. D. Hong, T. W. Sery, L. A. Donoso, L. J. Young, R. Bookstein, and E. Y. Lee. 1987. The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity. Nature 329: 642–645.
  • Lillemeier, B. F., M. Koster, and I. M. Kerr. 2001. STAT1 from the cell membrane to the DNA. EMBO J. 20: 2508–2517.
  • Lippincott-Schwartz, J., E. Snapp, and A. Kenworthy. 2001. Studying protein dynamics in living cells. Nat. Rev. Mol. Cell Biol. 2: 444–456.
  • 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., B. O. Petersen, K. Holm, J. Bartek, and K. Helin. 1996. Deregulated expression of E2F family members induces S-phase entry and overcomes p16INK4A-mediated growth suppression. Mol. Cell. Biol. 16: 1047–1057.
  • Mancini, M. A., B. Shan, J. A. Nickerson, S. Penman, and W. H. Lee. 1994. The retinoblastoma gene product is a cell cycle-dependent, nuclear matrix-associated protein. Proc. Natl. Acad. Sci. USA 91: 418–422.
  • Markiewicz, E., T. Dechat, R. Foisner, R. A. Quinlan, and C. J. Hutchison. 2002. Lamin A/C binding protein LAP2alpha is required for nuclear anchorage of retinoblastoma protein. Mol. Biol. Cell 13: 4401–4413.
  • McNally, J. G., W. G. Muller, D. Walker, R. Wolford, and G. L. Hager. 2000. The glucocorticoid receptor: rapid exchange with regulatory sites in living cells. Science 287: 1262–1265.
  • Mittnacht, S. 1998. Control of pRB phosphorylation. Curr. Opin. Genet. Dev. 8: 21–27.
  • Mittnacht, S., and R. A. Weinberg. 1991. G1/S phosphorylation of the retinoblastoma protein is associated with an altered affinity for the nuclear compartment. Cell 65: 381–393.
  • Morris, E. J., and N. J. Dyson. 2001. Retinoblastoma protein partners. Adv. Cancer Res. 82: 1–54.
  • Narita, M., S. Nunez, E. Heard, A. W. Lin, S. A. Hearn, D. L. Spector, G. J. Hannon, and S. W. Lowe. 2003. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113: 703–716.
  • Nevins, J. R. 2001. The Rb/E2F pathway and cancer. Hum. Mol. Genet. 10: 699–703.
  • Nielsen, S. J., R. Schneider, U. M. Bauer, A. J. Bannister, A. Morrison, D. O'Carroll, R. Firestein, M. Cleary, T. Jenuwein, R. E. Herrera, and T. Kouzarides. 2001. Rb targets histone H3 methylation and HP1 to promoters. Nature 412: 561–565.
  • Ozaki, T., M. Saijo, K. Murakami, H. Enomoto, Y. Taya, and S. Sakiyama. 1994. Complex formation between lamin A and the retinoblastoma gene product: identification of the domain on lamin A required for its interaction. Oncogene 9: 2649–2653.
  • Phair, R. D., and T. Misteli. 2000. High mobility of proteins in the mammalian cell nucleus. Nature 404: 604–609.
  • Qin, X. Q., T. Chittenden, D. M. Livingston, and W. G. Kaelin, Jr. 1992. Identification of a growth suppression domain within the retinoblastoma gene product. Genes Dev. 6: 953–964.
  • Reits, E. A., and J. J. Neefjes. 2001. From fixed to FRAP: measuring protein mobility and activity in living cells. Nat. Cell Biol. 3: E145–E147.
  • Robertson, K. D., S. Ait-Si-Ali, T. Yokochi, P. A. Wade, P. L. Jones, and A. P. Wolffe. 2000. DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters. Nat. Genet. 25: 338–342.
  • Rowland, B. D., S. G. Denissov, S. Douma, H. G. Stunnenberg, R. Bernards, and D. S. Peeper. 2002. E2F transcriptional repressor complexes are critical downstream targets of p19(ARF)/p53-induced proliferative arrest. Cancer Cell 2: 55–65.
  • Schlisio, S., T. Halperin, M. Vidal, and J. R. Nevins. 2002. Interaction of YY1 with E2Fs, mediated by RYBP, provides a mechanism for specificity of E2F function. EMBO J. 21: 5775–5786.
  • Schwille, P. 2001. Fluorescence correlation spectroscopy and its potential for intracellular applications. Cell Biochem. Biophys. 34: 383–408.
  • Sever-Chroneos, Z., S. P. Angus, A. F. Fribourg, H. Wan, I. Todorov, K. E. Knudsen, and E. S. Knudsen. 2001. Retinoblastoma tumor suppressor protein signals through inhibition of cyclin-dependent kinase 2 activity to disrupt PCNA function in S phase. Mol. Cell. Biol. 21: 4032–4045.
  • Sherr, C., and F. McCormick. 2002. The RB and p53 pathways in cancer. Cancer Cell 2: 103–112.
  • Sherr, C. J. 2001. The INK4a/ARF network in tumour suppression. Nat. Rev. Mol. Cell Biol. 2: 731–737.
  • Sherr, C. J., and J. M. Roberts. 1999. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 13: 1501–1512.
  • Siddiqui, H., D. A. Solomon, R. W. Gunawardena, Y. Wang, and E. S. Knudsen. 2003. Histone deacetylation of RB-responsive promoters: requisite for specific gene repression but dispensable for cell cycle inhibition. Mol. Cell. Biol. 23: 7719–7731.
  • Stenoien, D. L., K. Patel, M. G. Mancini, M. Dutertre, C. L. Smith, B. W. O'Malley, and M. A. Mancini. 2001. FRAP reveals that mobility of oestrogen receptor-alpha is ligand- and proteasome-dependent. Nat. Cell Biol 3: 15–23.
  • Strobeck, M. W., K. E. Knudsen, A. F. Fribourg, M. F. DeCristofaro, B. E. Weissman, A. N. Imbalzano, and E. S. Knudsen. 2000. BRG-1 is required for RB-mediated cell cycle arrest. Proc. Natl. Acad. Sci. USA 97: 7748–7753.
  • Strobeck, M. W., D. N. Reisman, R. W. Gunawardena, B. L. Betz, S. P. Angus, K. E. Knudsen, T. F. Kowalik, B. E. Weissman, and E. S. Knudsen. 2002. Compensation of BRG-1 function by Brm: insight into the role of the core SWI-SNF subunits in retinoblastoma tumor suppressor signaling. J. Biol. Chem. 277: 4782–4789.
  • Takahashi, Y., J. B. Rayman, and B. D. Dynlacht. 2000. Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression. Genes Dev. 14: 804–816.
  • Takemura, M., F. Ohoka, M. Perpelescu, M. Ogawa, H. Matsushita, T. Takaba, T. Akiyama, H. Umekawa, Y. Furuichi, P. R. Cook, and S. Yoshida. 2002. Phosphorylation-dependent migration of retinoblastoma protein into the nucleolus triggered by binding to nucleophosmin/B23. Exp. Cell Res. 276: 233–241.
  • Templeton, D. J., S. H. Park, L. Lanier, and R. A. Weinberg. 1991. Nonfunctional mutants of the retinoblastoma protein are characterized by defects in phosphorylation, viral oncoprotein association, and nuclear tethering. Proc. Natl. Acad. Sci. USA 88: 3033–3037.
  • van Lohuizen, M. 1999. The trithorax-group and polycomb-group chromatin modifiers: implications for disease. Curr. Opin. Genet. Dev. 9: 355–361.
  • Visintin, R., and A. Amon. 2000. The nucleolus: the magician's hat for cell cycle tricks. Curr. Opin. Cell Biol. 12: 372–377.
  • Wang, J. Y., E. S. Knudsen, and P. J. Welch. 1994. The retinoblastoma tumor suppressor protein. Adv. Cancer Res. 64: 25–85.
  • Weintraub, S. J., K. N. Chow, R. X. Luo, S. H. Zhang, S. He, and D. C. Dean. 1995. Mechanism of active transcriptional repression by the retinoblastoma protein. Nature 375: 812–815.
  • Wells, J., K. E. Boyd, C. J. Fry, S. M. Bartley, and P. J. Farnham. 2000. Target gene specificity of E2F and pocket protein family members in living cells. Mol. Cell. Biol. 20: 5797–5807.
  • Wells, J., P. S. Yan, M. Cechvala, T. Huang, and P. J. Farnham. 2003. Identification of novel pRb binding sites using CpG microarrays suggests that E2F recruits pRb to specific genomic sites during S phase. Oncogene 22: 1445–1460.
  • White, R. J. 1997. Regulation of RNA polymerases I and III by the retinoblastoma protein: a mechanism for growth control? Trends Biochem. Sci. 22: 77–80.
  • Xiao, Z. X., J. Chen, A. J. Levine, N. Modjtahedi, J. Xing, W. R. Sellers, and D. M. Livingston. 1995. Interaction between the retinoblastoma protein and the oncoprotein MDM2. Nature 375: 694–698.
  • Yang, H., B. O. Williams, P. W. Hinds, T. S. Shih, T. Jacks, R. T. Bronson, and D. M. Livingston. 2002. Tumor suppression by a severely truncated species of retinoblastoma protein. Mol. Cell. Biol. 22: 3103–3110.
  • Zacksenhaus, E., R. Bremner, R. A. Phillips, and B. L. Gallie. 1993. A bipartite nuclear localization signal in the retinoblastoma gene product and its importance for biological activity. Mol. Cell. Biol. 13: 4588–4599.
  • Zhang, H. S., M. Gavin, A. Dahiya, A. A. Postigo, D. Ma, R. X. Luo, J. W. Harbour, and D. C. Dean. 2000. Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF. Cell 101: 79–89.
  • Zhang, H. S., A. A. Postigo, and D. C. Dean. 1999. Active transcriptional repression by the Rb-E2F complex mediates G1 arrest triggered by p16INK4a, TGFbeta, and contact inhibition. Cell 97: 53–61.

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