Abstract
The Retinoblastoma family consists of three genes, RB, p107, and Rb2/p130, all fundamental in the control of important cellular phenomena, such as cell cycle, differentiation, and apoptosis. The “founder” and the most investigated gene of the family is RB, which is considered the prototype for the tumor suppressor genes (1,2). The other two genes, p107 and Rb2/p130, and the proteins they code for, p107 and pRb2/p130, respectively, clearly reflect a high degree of structural and functional similarity to the RB gene product, pRb (3,4). The RB family proteins were disclosed initially by investigators working on viral oncoproteins. In particular, a set of proteins associated with the Adenovirus 5 E1A oncoprotein was identified, and the bands representing the most abundant ones were named p60, p105, p107, p130, and p300, in keeping with their apparent molecular mass, as determined by SDS-PAGE (5). The subsequent characterization of these proteins identified p105 as the product of the RB gene (6). Later, genes encoding p107 (7,8) and pRb2/p130 (9–11) were cloned using different strategies.
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References
Weinberg, R. A. (1991) Tumor suppressor genes. Science 254, 1138–1146.
Hinds, P. W. and Weinberg, R. A. (1994) Tumor suppressor genes. Curr. Opin. Genet. Dev. 4, 135–141.
Paggi, M. G., Baldi, A., Bonetto, F., and Giordano, A. (1996) Retinoblastoma protein family in cell cycle and cancer: a review. J. Cell. Biochem. 62, 418–430.
Mulligan, G. and Jacks, T. (1998) The retinoblastoma gene family: cousins with overlapping interests. Trends Genet. 14, 223–229.
Harlow, E., Whyte, P., Franza, B. R., Jr., and Schley, C. (1986) Association of adenovirus early-region 1A proteins with cellular polypeptides. Mol. Cell. Biol. 6, 1579–1589.
Whyte, P., Buchkovich, K. J., Horowitz, J. M., et al. (1988) Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product. Nature 334, 124–129.
Ewen, M. E., Xing, Y. G., Lawrence, J. B., and Livingston, D. M. (1991) Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein. Cell 66, 1155–1164.
Zhu, L., van den Heuvel, S., Helin, K., et al. (1993) Inhibition of cell proliferation by p107, a relative of the retinoblastoma protein. Genes Dev. 7, 1111–1125.
Mayol, X., Graña, X., Baldi, A., Sang, N., Hu, Q., and Giordano, A. (1993) Cloning of a new member of the retinoblastoma gene family (pRb2) which binds to the E1A transforming domain. Oncogene 8, 2561–2566.
Li, Y., Graham, C., Lacy, S., Duncan, A. M., and Whyte, P. (1993) The adenovirus E1A-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E. Genes Dev. 7, 2366–2377.
Hannon, G. J., Demetrick, D., and Beach, D. (1993) Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins. Genes Dev. 7, 2378–2391.
Ewen, M. E. (1994) The cell cycle and the retinoblastoma protein family. [Review]. Cancer Metastasis Rev. 13, 45–66.
Weinberg, R. A. (1995) The retinoblastoma protein and cell cycle control. Cell 81, 323–330.
Harbour, J. W. and Dean, D. C. (2000) The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev. 14, 2393–2409.
DeCaprio, J. A., Ludlow, J. W., Figge, J., et al. (1988) SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 54, 275–283.
Dyson, N., Buchkovich, K., Whyte, P., and Harlow, E. (1989) The cellular 107K protein that binds to adenovirus E1A also associates with the large T antigens of SV40 and JC virus. Cell 58, 249–255.
Dyson, N., Howley, P. M., Munger, K., and Harlow, E. (1989) The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 243, 934–937.
Marsilio, E., Cheng, S. H., Schaffhausen, B., Paucha, E., and Livingston, D. M. (1991) The T/t common region of simian virus 40 large T antigen contains a distinct transformation-governing sequence. J. Virol. 65, 5647–5652.
Dyson, N., Guida, P., Munger, K., and Harlow, E. (1992) Homologous sequences in adenovirus E1A and human papillomavirus E7 proteins mediate interaction with the same set of cellular proteins. J. Virol. 66, 6893–6902.
Ludlow, J. W. and Skuse, G. R. (1995) Viral oncoprotein binding to pRB, p107, p130, and p300. Virus Res. 35, 113–121.
Goodrich, D. W., Wang, N. P., Qian, Y. W., Lee, E. Y., and Lee, W. H. (1991) The retinoblastoma gene product regulates progression through the G1 phase of the cell cycle. Cell 67, 293–302.
Starostik, P., Chow, K. N. B., and Dean, D. C. (1996) Transcriptional repression and growth suppression by the p107 pocket protein. Mol. Cell. Biol. 16, 3606–3614.
Claudio, P. P., Howard, C. M., Baldi, A. et al. (1994) p130/pRb2 has growth suppressive properties similar to yet distinctive from those of retinoblastoma family members pRb and p107. Cancer Res. 54, 5556–5560.
Lee, W. H., Shew, J. Y., Hong, F. D., et al. (1987) The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity. Nature 329, 642–645.
Buchkovich, K., Duffy, L. A., and Harlow, E. (1989) The retinoblastoma protein is phosphorylated during specific phases of the cell cycle. Cell 58, 1097–1105.
Mittnacht, S. and Weinberg, R. A. (1991) G1/S phosphorylation of the retinoblastoma protein is associated with an altered affinity for the nuclear compartment. Cell 65, 381–393.
Chen, P. L., Scully, P., Shew, J. Y., Wang, J. Y., and Lee, W. H. (1989) Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation. Cell 58, 1193–1198.
DeCaprio, J. A., Ludlow, J. W., Lynch, D., et al. (1989) The product of the retinoblastoma susceptibility gene has properties of a cell cycle regulatory element. Cell 58, 1085–1095.
Mihara, K., Cao, X. R., Yen, A., et al. (1989) Cell cycle-dependent regulation of phosphorylation of the human retinoblastoma gene product. Science 246, 1300–1303.
MacLachlan, T. K., Sang, N., and Giordano, A. (1995) Cyclins, cyclin-dependent kinases and Cdk inhibitors: implications in cell cycle control and cancer. Eukariotic Gene Expr. 5, 127–156.
Beijersbergen, R. L., Carlée, L., Kerkhoven, R. M., and Bernards, R. (1995) Regulation of the retinoblastoma protein-related p107 by G1 cyclin complexes. Genes Dev. 9, 1340–1353.
Faha, B., Ewen, M. E., Tsai, L. H., Livingston, D. M., and Harlow, E. (1992) Interaction between human cyclin A and adenovirus E1A-associated p107 protein. Science 255, 87–90.
Lees, E., Faha, B., Dulic, V., Reed, S. I., and Harlow, E. (1992) Cyclin E/cdk2 and cyclin A/cdk2 kinases associate with p107 and E2F in a temporally distinct manner. Genes Dev. 6, 1874–1885.
Baldi, A., De Luca, A., Claudio, P. P., et al. (1995) The Rb2/p130 gene product is a nuclear protein whose phosphorylation is cell cycle regulated. J. Cell Biochem. 59, 402–408.
Cobrinik, D., Whyte, P., Peeper, D. S., Jacks, T., and Weinberg, R. A. (1993) Cell cycle-specific association of E2F with the p130 E1A-binding protein. Genes Dev. 7, 2392–2404.
Claudio, P. P., De Luca, A., Howard, C. M., et al. (1996) Functional analysis of pRb2/p130 interaction with cyclins. Cancer Res. 56, 2003–2008.
Riley, D. J., Lee, E. Y. H. P., and Lee, W.-H. (1994) The retinoblastoma protein: more than a tumor suppressor. Annu. Rev. Cell Biol. 10, 1–29.
Sidle, A., Palaty, C., Dirks, P., et al. (1996) Activity of the retinoblastoma family proteins, pRB, p107, and p130, during cellular proliferation and differentiation. Crit. Rev. Biochem. Mol. Biol. 31, 237–271.
Herwig, S. and Strauss, M. (1997) The retinoblastoma protein: a master regulator of cell cycle, differentiation and apoptosis. Eur. J. Biochem. 246, 581–601.
Stiegler, P., Kasten, M., and Giordano, A. (1998) The RB family of cell cycle regulatory factors. J. Cell Biochem. 30–31, 30–36.
Sherr, C. J. (2000) The Pezcoller lecture: cancer cell cycles revisited. Cancer Res. 60, 3689–3695.
Yeung, R. S., Bell, D. W., Testa, J. R., et al. (1993) The retinoblastoma-related gene, RB2, maps to human chromosome 16q12 and rat chromosome 19. Oncogene 8, 3465–3468.
Yandell, D. W., Campbell, T. A., Dayton, S. H., et al. (1989) Oncogenic point mutations in the human retinoblastoma gene: their application to genetic counseling. N. Engl. J. Med. 321, 1689–1695.
Zacksenhaus, E., Bremner, R., Phillips, R. A., and Gallie, B. L. (1993) A bipartite nuclear localization signal in the retinoblastoma gene product and its importance for biological activity. Mol. Cell Biol. 13, 4588–4599.
Cinti, C., Claudio, P. P., Howard, C. M., et al. (2000) Genetic alterations disrupting the nuclear localization of the retinoblastoma-related gene RB2/p130 in human tumor cell lines and primary tumors. Cancer Res. 60, 383–389.
Zerler, B., Moran, B., Maruyama, K., Moomaw, J., Grodzicker, T., and Ruley, H. E. (1986) Adenovirus E1A coding sequences that enable ras and pmt oncogenes to transform cultured primary cells. Mol. Cell Biol. 6, 887–899.
Beijersbergen, R. L. and Bernards, R. (1996) Cell cycle regulation by the retinoblastoma family of growth inhibitory proteins. Biochim. Biophys. Acta Rev. Cancer 1287, 103–120.
Paggi, M. G., Martelli, F., Fanciulli, M., et al. (1994) Defective human retinoblastoma protein identified by lack of interaction with the E1A oncoprotein. Cancer Res. 54, 1098–1104.
Bignon, Y. J., Shew, J. Y., Rappolee, D., et al. (1990) A single Cys706 to Phe substitution in the retinoblastoma protein causes the loss of binding to SV40 T antigen. Cell Growth Differ. 1, 647–651.
Ting, A. and Morris, P. J. (1971) A technique for lymphocyte preparation from stored heparinized blood. Vox Sang. 20, 561–563.
Mancini, M. A., Shan, B., Nickerson, J. A., Penman, S., and Lee, W. H. (1994) The retinoblastoma gene product is a cell cycle-dependent, nuclear matrix-associated protein. Proc. Natl. Acad. Sci. USA 91, 418–422.
Laemmli, U. K. (1970) Cleavage of structural proteins during the assembly of the head of the bacteriophage T4. Nature 227, 680–685.
Paggi, M. G., De Fabritiis, P., Bonetto, F., et al. (1995) The retinoblastoma gene product in acute myeloid leukemia: A possible involvement in promyelocytic leukemia. Cancer Res. 55, 4552–4556.
Valente, P., Melchiori, A., Paggi, M. G., et al. (1996) RB1 oncosuppressor gene over-expression inhibits tumor progression and induces melanogenesis in metastatic melanoma cells. Oncogene 13, 1169–1178.
Olopade, O. I., Jenkins, R. B., Ransom, D. T., et al. (1992) Molecular analysis of deletions of the short arm of chromosome 9 in human gliomas. Cancer Res. 52, 2523–2529.
Lukas, J., Parry, D., Aagaard, L., et al. (1995) Retinoblastoma-protein-dependent cell-cycle inhibition by the tumour suppressor p16. Nature 375, 503–506.
Shew, J. Y., Lin, B. T., Chen, P. L., Tseng, B. Y., Yang Feng, T. L., and Lee, W. H. (1990) C-terminal truncation of the retinoblastoma gene product leads to functional inactivation. Proc. Natl. Acad. Sci. USA 87, 6–10.
A. K. Furr, ed. CRC Handbook of Laboratory Safety, (1995). CRC Press, Boca Raton, FL.
Baldi, A., Esposito, V., De Luca, A., et al. (1997) Differential expression of Rb2/p130 and p107 in normal human tissues and in primary lung cancer. Clin. Cancer Res. 3, 1691–1697.
Helin, K., Holm, K., Niebuhr, A., et al. (1997) Loss of the retinoblastoma protein-related p130 protein in small cell lung carcinoma. Proc. Natl. Acad. Sci. USA. 94, 6933–6938.
Susini, T., Baldi, F., Howard, C. M., et al. (1998) Expression of the retinoblastoma-related gene Rb2/p130 correlates with clinical outcome in endometrial cancer. J. Clin. Oncol. 16, 1085–1093.
Massaro-Giordano, M., Baldi, G., De Luca, A., Baldi, A., and Giordano, A. (1999) Differential expression of the retinoblastoma gene family members in choroidal melanoma: prognostic significance. Clin. Cancer Res. 5, 1455–1458.
Leoncini, L., Bellan, C., Cossu, A., et al. (1999) Retinoblastoma-related p107 and pRb2/p130 proteins in malignant lymphomas: distinct mechanisms of cell growth control. Clin. Cancer Res. 5, 4065–4072.
Zamparelli, A., Masciullo, V., Bovicelli, A., et al. (2001) Expression of cell-cycle-associated proteins pRb2/p130 and p27kip1 in vulvar squamous cell carcinomas. Hum. Pathol. 32, 4–9.
Mutti, L., De Luca, A., Claudio, P. P., Convertino, G., Carbone, M., and Giordano, A. (1998) Simian virus 40-like DNA sequences and large-T antigen-retinoblastoma family protein pRb2/p130 interaction in human mesothelioma. Dev. Biol. Stand. 94, 47–53.
Claudio, P. P., Howard, C. M., Pacilio, C., et al. (2000) Mutations in the retinoblastoma-related gene RB2/p130 in lung tumors and suppression of tumor growth in vivo by retrovirus-mediated gene transfer. Cancer Res. 60, 372–382.
Claudio, P. P., Howard, C. M., Fu, Y., et al. (2000) Mutations in the retinoblastoma-related gene RB2/p130 in primary nasopharyngeal carcinoma. Cancer Res. 60, 8–12.
Ichimura, K., Hanafusa, H., Takimotol H, Ohgama, Y., Akagi, T., and Shimizu, K. (2000) Structure of the human retinoblastoma-related p107 gene and its intragenic deletion in a B-cell lymphoma cell line. Gene 251, 37–43.
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Paggi, M.G., Felsani, A., Giordano, A. (2003). Growth Control by the Retinoblastoma Gene Family. In: El-Deiry, W.S. (eds) Tumor Suppressor Genes. Methods in Molecular Biology™, vol 222. Humana Press, Totowa, NJ. https://doi.org/10.1385/1-59259-328-3:003
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DOI: https://doi.org/10.1385/1-59259-328-3:003
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