The retinoblastoma tumour suppressor in development and cancer

Nature Reviews Cancer

Volumn 2, Issue 12, 2002, Pages 910-917

  Classon, Marie ^a   Harlow, Ed ^b  

^a MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

RETINOBLASTOMA PROTEIN; TUMOR SUPPRESSOR PROTEIN; NUCLEAR PROTEIN; PHOSPHOPROTEIN; PROTEIN; PROTEIN P107; PROTEIN P130; RBL1 PROTEIN, MOUSE; RBL2 PROTEIN, HUMAN; RBL2 PROTEIN, MOUSE;

ANTINEOPLASTIC ACTIVITY; CANCER RESEARCH; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL SURVIVAL; DRUG MECHANISM; DRUG RESEARCH; EVIDENCE BASED MEDICINE; KNOCKOUT MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; RETINOBLASTOMA; REVIEW; ANIMAL; CELL DIVISION; GENETICS; HUMAN; METABOLISM; MOUSE; MOUSE MUTANT; PATHOLOGY; PHENOTYPE; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR GENE;

ANIMALS; CELL DIVISION; GENES, RETINOBLASTOMA; HUMANS; MICE; MICE, KNOCKOUT; NUCLEAR PROTEINS; PHENOTYPE; PHOSPHOPROTEINS; PROTEINS; RETINOBLASTOMA; RETINOBLASTOMA PROTEIN; RETINOBLASTOMA-LIKE PROTEIN P107; RETINOBLASTOMA-LIKE PROTEIN P130; SIGNAL TRANSDUCTION;

EID: 0036884829     PISSN: 1474175X     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrc950     Document Type: Review

References (132)

1. Hungerford, D. A. Some early studies of human chromosomes, 1879-1955 Cytogenet. Cell Genet 20, 1-11 (1978).
2. Knudson, A. G. Jr. Retinoblastoma: a prototypic hereditary neoplasm. Semin. Oncol 5, 57-60 (1978).
3. Friend, S. H. et al. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323, 643-646 (1986).
4. Lee, W. H. et al. Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science 235, 1394-1399 (1987).
5. Fung, Y. K. et al. Structural evidence for the authenticity of the human retinoblastoma gene. Science 236, 1657-1661 (1987).
6. Weinberg, R. A. Tumor suppressor genes. Science 254, 1138-1146 (1991).
7. Whyte, P. et al. Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product. Nature 334, 124-129 (1988).
8. DeCaprio, J. A. et al. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 54, 275-283 (1988). References 7 and 8 provided the first description of RB interaction with a viral oncogene - adenovirus E1A and SV40 T Ag; these findings laid the foundation for studies of RB's role in cell-cycle control.
9. Munger, K. et al. Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. EMBO J. 8, 4099-4105 (1989).
10. Dyson, N. & Harlow, E., eds. (1992). Adenovirus E1A targets key regulators of cell proliferation. (Imperial Cancer Research Fund). [Au: please provide full reference]
11. Qin, X. Q., Chittenden, T., Livingston, D. M. & Kaelin, W. G. Jr. Identification of a growth suppression domain within the retinoblastoma gene product. Genes Dev. 6, 953-964 (1992).
12. Huang, H. J. et al. Suppression of the neoplastic phenotype by replacement of the RB gene in human cancer cells. Science 242, 1563-1566 (1988).
13. Goodrich, D. W., Wang, N. P., Qian, Y.-W., Lee, E. Y.-H. P. & Lee, W.-H. The retinoblastoma gene product regulates progression through the G1 phase of the cell cycle. Cell 67, 293-302 (1991).
14. Herrera, R. E. et al. Altered cell cycle kinetics, gene expression, and G1 restriction point regulation in Rb-deficient fibroblasts. Mol. Cell. Biol. 16, 2402-2407 (1996).
15. Hurford, R., Cobrinik, D., Lee, M.-H. & Dyson, N. pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes. Genes Dev. 11, 1447-1463 (1997).
16. Classon, M. et al. Combinatorial roles for pRB, p107 and p130 in E2F-mediated cell cycle control. Proc. Natl Acad. Sci. USA 97, 10820-10825 (2000).
17. Helin, K. et al. A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F. Cell 70, 337-350 (1992).
18. Kaelin, W. G. Jr et al. Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties. Cell 70, 351-364 (1992).
19. Shan, B., Durfee, T. & Lee, W.-H. Disruption of RB/E2F-1 interaction by single point mutations in E2F-1 enhances S-phase entry and apoptosis. Proc. Natl Acad. Sci. USA 93, 679-684 (1996).
20. Newns, J. R. E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. Science 258, 424-429 (1992).
21. Dyson, N. The regulation of E2F by pRB-family proteins. Genes Dev. 12, 2245-2262 (1998).
22. Trimarchi, J. M. & Lees, J. A. Sibling rivalry in the E2F family. Nature Rev. Mol. Cell Biol. 3, 11-20 (2002).
23. Fattaey, A., Helin, K. & Harlow, E. Transcriptional inhibition by the retinoblastoma protein. - Phil. Trans. R. Soc. Lond. B 340, 333-336 (1993).
24. Helin, K., Harlow, E. & Fattaey, A. Inhibition of E2F-1 transactivation by direct binding of the retinoblastoma protein. Mol. Cell. Biol. 13, 6501-6508 (1993).
25. Johnson, D. G., Ohtani, K. & Nevins, J. R. Autoregulatory control of E2F-1 expression in response to positive and negative regulators of cell cycle expression. Genes Dev. 8, 1514-1525 (1994).
26. Weintraub, S. J., Prater, C. A. & Dean, D. C. Retinoblastoma protein switches the E2F site from positive to negative element. Nature 358, 259-261 (1992). The first study that suggested a role for RB as an active transcriptional repressor, later shown more directly (see reference 27).
27. Weintraub, S. J. et al. Mechanism of active transcriptional repression by the retinoblastoma protein. Nature 375, 812-815 (1995).
28. Nevins, J. Toward an understanding of the functional complexity of the E2F and retinoblastoma families. Cell Growth Differ. 9, 585-593 (1998).
29. Flemington, E. K., Speck, S. H. & Kaelin, J., W. G. E2F-1-mediated transactivation is inhibited by complex formation with the retinoblastoma susceptibility gene product. Proc. Natl Acad. Sci. USA 90, 6914-6918 (1993).
30. Bremner, R. et al. A. Direct transcriptional repression by pRB and its reversal by specific cyclins. Mol. Cell. Biol. 15, 3256-3265 (1995).
31. Adnane, J., Shao, Z. & Robbins, P. D. The retinoblastoma susceptibility gene product represses transcription when directly bound to the promoter. J. Biol. Chem. 270, 8837-8843 (1995).
32. Harbour, J. W. & Dean, D. C. Chromatin remodeling and Rb activity. Curr. Opin. Cell Biol. 12, 685-689 (2000).
33. Harbour, J. W. & Dean, D. C. Corepressors and retinoblastoma protein function. Curr. Top. Microbiol. Immunol. 254, 137-144 (2001).
34. Brehm, A. & Kouzarides, T. Retinoblastoma protein meets chromatin. Trends Biochem. Sci. 24, 142-145 (1999).
35. Buchkovich, K., Duffy, L. A. & Harlow, E. The retinoblastoma protein is phosphorylated during specific phases of the cell cycle. Cell 58, 1097-1105 (1989).
36. Cooper, S. & Shayman, J. A. Revisiting retinoblastoma protein phosphorylation during the mammalian cell cycle. Cell. Mol. Life. Sci. 58, 580-595 (2001).
37. Sherr, C. J. Cancer cell cycles Science 274, 1672-1677 (1998).
38. Kennedy, B., Barbie, D., Classon, M., Dyson, N. & Harlow, E. Nuclear organization of DNA replication in primary mammalian cells. Genes Dev. 15, 2855-2868 (2000).
39. Royzman, I., Austin, R. J., Bosco, G., Bell, S. R. & Orr-Weaver, T.L. ORC localization in Drosophila follicle cells and the effects of mutations in dE2F and dDP. Genes Dev. 13, 827-840 (1999).
40. Bosco, G., Du, W. & Orr-Weaver, T. DNA replication control through interaction of E2F-RB and the origin recognition complex. Nature Cell Biol. 3, 289-295 (2001). References 38 and 40 indicate a direct role for RB in DNA replication.
41. Lipinski, M. M. & Jacks, T. The retinoblastoma gene family in differentiation and development. Oncogene 18, 7873-7882 (1999).
42. Hickman, E. S., Moroni, M. C. & Helin, K. The role of p53 and Rb in apoptosis and cancer. Curr. Opin. Genet. Dev. 12, 60-66 (2002).
43. Wu, X. & Levine, A. J. p53 and E2F-1 cooperate to mediate apoptosis. Proc. Natl Acad. Sci. USA 91, 3602-3606 (1994).
44. Qin, X.-Q., Livingston, D. M., Kaelin, W. G. J. & Adams, P. Deregulated transcription factor E2F-1 expression leads to S-phase entry and p53-mediated apoptosis. Proc. Natl Acad. Sci. USA 91, 10918-10922 (1994).
45. Shan, B. & Lee, W.-H. Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis, Mol. Cell. Biol. 14, 8166-8173 (1994). References 43-45 first indicated a positive role for E2F1 in inducing apoptosis, raising the possibility that RB could have anti-apoptotic functions.
46. Guo, Z., Yikang, S., Yoshida, H., Mak, T. W. & Zacksenhaus, E. Inactivation of the retinoblastoma tumor suppressor induces Apaf-1 dependent and independent apoptotic pathways during embryogenesis. Cancer Res. 61, 8395-8400 (2001).
47. Ishida, S. et al. Role for E2F in control of both DNA replication and mitotic functions as revealed from DNA microarray analysis. Mol. Cell. Biol. 21, 4684-4699 (2001).
48. Moroni, M. et al. Apaf-1 is a transcriptional target for E2F and p53. Nature Cell Biol. 3, 552-558 (2001).
49. Muller, H. et al. E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis. Genes Dev. 15, 267-285 (2001).
50. Morris, E. J. & Dyson, N. J. Retinoblastoma protein partners. Adv. Cancer Res. 82, 1-54 (2001).
51. Mulligan, G. & Jacks, J. The retinoblastoma gene family: cousins with overlapping interests. Trends Genet. 14, 223-229 (1998).
52. Classon, M. & Dyson, N. p107 and p130: versatile proteins with interesting pockets. Exp. Cell Res. 264, 135-147 (2001).
53. Zhu, L. et al. Growth suppression by members of the retinoblastoma protein family. Cold Spring Herb. Symp. Quant. Biol. 59, 75-84 (1994).
54. Zhu, L. et al. The pRB-related protein p107 contains two growth suppression domains: Independent interactions with E2F and cyclin/cdk complexes. EMBO J. 14, 904-1913, (1995).
55. Dynlacht, B. D., Moberg, K., Lees, J. A., Harlow, E. & Zhu, L. Specific regulation of E2F family members by cyclin-dependent kinase. Mol. Cell. 17, 3867-3875 (1997).
56. CIP1-related domain to bind cyclin/cdk2 and regulate interactions with E2F. Genes Dev. 9, 1740-1752 (1995).
57. Jiang, Z., Guo, Z., Saad, F. & Zacksenhaus, E. Retinoblastoma gene promoter directs transgene expression exclusively to the nervous system. J. Biol. Chem. 276, 593-600 (2001).
58. Zacksenhaus, E. et al. pRb controls proliferation, differentiation, and death of skeletal muscle cells and other lineages during embryogenesis. Genes Dev. 10, 3051-3064 (1996).
59. Jacks, et al. Effects of an Rb mutation in the mouse. Nature 359, 295-300 (1992).
60. Lee, E. Y. et al. Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis. Nature 359, 288-294 (1992). References 58-60 explore the developmental consequences of loss of Rb in mice, and indicate that Rb is important in proliferation, apototosis and differentiation during development.
61. Morgenbesser, S. D., Williams, B. O., Jacks, T. & De Pinho, R. A. p53-dependent apoptosis produced by Rb-deficiency in the developing lens. Nature 371, 72-74 (1994).
62. Jacks, T. Tumor suppressor gene mutations in mice. Annu. Rev. Genet. 30, 603-636 (1996).
63. Herrera, R. E., Makela, T. P. & Weinberg, R. A. TGFβ-induced growth inhibition in primary fibroblasts requires the retinoblastoma protein. Mol. Biol. Cell. 7, 1335-1342 (1996).
64. Harrington, E. A., Bruce, J. L., Harlow, E. & Dyson, N. pRB plays an essential role in cell cycle arrest induced by DNA damage. Proc. Natl Acad. Sci. USA 95, 11945-11960 (1998).
65. Brugarolas, J. et al. Inhibition of cyclin-dependent kinase 2 by p21 is necessary for retinoblastoma protein-mediated G1 arrest after γ-irradiation. Proc. Natl Acad. Sci. USA 96, 1002-1007(1999). The experiments described in references 64 and 65 indicate a role for RB in DNA-damage-induced G1 arrest.
66. Classon, M., Kennedy, B. K., Mulloy, R. & Harlow, E. E. Opposing roles for pRB and p107 in adipocyte differentiation. Proc. Natl Acad. Sci. USA 97, 10826-10831 (2000).
67. Chen, P.-L., Riley, D. J., Chen, Y. & Lee, W.-H. Retinoblastoma protein positively regulates terminal adipocyte differentiation through direct interaction with C/EBPs, Genes Dev. 10, 2794-2804 (1996).
68. Novitch, B. G., Mulligan, G. J., Jacks, T. & Lassar, A. B. Skeletal muscle cells lacking the retinoblastoma protein display defects in muscle gene expression and accumulate in S and G2 phases of the cell cycle. J. Cell Biol. 135, 441-456 (1996).
69. Novitch, B., Spicer, D., Kim, P., Cheung, W. & Lassar, A. pRb is required for MEF2-dependent gene expression as well as cell-cycle arrest during skeletal muscle differentiation. Curr. Biol. 9, 449-459 (1999).
70. Gu, W. et al. Interaction of myogenic factors and the retinoblastoma protein mediates muscle cell commitment and differentiation. Cell 72, 309-324 (1993).
71. Puri, P. L. et al. Class I histone deacetylases sequentially interact with MyoD and pRB during skeletal myogenesis. Mol. Cell. 8, 885-897 (2001).
72. Chen, P. L., Riley, D. J., Chen-Kiang, S. & Lee, W. H. Retinoblastoma protein directly interacts with and activates the transcription factor NF-IL6. Proc. Natl Acad. Sci. USA 93, 465-469 (1996).
73. Sellers, W. R. et al. Stable binding to E2F is not required for the retinoblastoma protein to activate transcription, promote differentiation, and suppress tumor cell growth. Genes Dev. 12, 95-106 (1998).
74. Kowalik, T. F., DeGregori, J., Schwarz, J. K. & Nevins, J. R. E2F1 overexpression in quiescent fibroblasts leads to induction of cellular DNA synthesis and apoptosis. J. Virol. 69, 2491-2500 (1995).
75. DeGregori, J., Leone, G., Miron, A., Jakoi, L. & Nevins, J. R. Distinct roles for E2F proteins in cell growth control and apoptosis. Proc. Natl Acad. Sci. USA 94, 7245-7250 (1997).
76. Zieboid, U., Reza, T., Caron, A. & Lees, J. A. E2F3 contributes both to the inappropriate proliferation and to the apoptosis arising in Rb mutant embryos. Genes Dev. 15, 386-391 (2001).
77. Tsai, K. Y. et al. Mutation of E2F1 suppresses apoptosis and inappropriate S-phase entry and extends survival of Rb-deficient mouse embryos. Mol. Cell. 2, 293-304 (1998).
78. Guo, Z., Yikang, S., Yoshida, H., Mak, T. & Zacksenhaus, E. Inactivation of the retinoblastoma tumor suppressor induces Apaf-1 dependent and independent apoptotic pathways during embryogenesis. Cancer Res. 61, 8395-8400 (2001).
79. Simpson, M. T. W. et al. Caspase 3 deficiency rescues peripheral nervous system defect in retinoblastom nullizygous mice. J. Neurosci. 21, 7089-7098 (2001).
80. Iavarone, A., Garg, P., Lasorella, A., Hsu, J. & Israel, M. A. The helix-loop-helix protein Id-2 enhances cell proliferation and binds to the retinoblastoma protein. Genes Dev. 8, 1270-1284 (1994).
81. Lasorella, A., Noseda, M., Beyna, M. & Iavarone, A. Id2 is a retinoblastoma protein target and mediates signalling by Myc oncoproteins. Nature 407, 592-598, (2000).
82. Lipinski, M., MacLeod, K., Williams, B., Mullaney, T., Crowley, D. & Jacks, T. Cell-autononomous and non-cell-autonomous functions of the Rb tumor suppressor in developing central nervous system. EMBO J. 20, 3402-3413 (2001).
83. Williams, B. O. et al. Extensive contribution of Rb-deficient cells to adult chimeric mice with limited histopathological consequences. EMBO J. 13, 4251-4259 (1994).
84. Maandag, E. C. R. et al. Developmental rescue of an embryonic-lethal mutation in the retinoblastoma gene in chimeric mice. EMBO J. 13, 4260-4268 (1994).
85. Voojis, M. & Berns, A. Developmental defects and tumor predisposition in Rb mutant mice. Oncogene 18, 5293-5303 (1999).
86. Whyatt, D. & Grosveld, F. Cell-nonautonomous function of the retinoblastoma tumor suppressor protein: new interpretations of old phenotypes. EMBO J. 3, 130-135 (2002).
87. Ferguson, K. L. et al. Telencephalon-specific Rb knockouts reveal enhanced neurogenesis, survival and abnormal cortical development. EMBO J. 21, 3337-3346 (2002).
88. Cobrinik, D. et al. Shared role of the pRB-related p130 and p107 proteins in limb development. Genes Dev. 10, 1633-1644 (1996).
89. Lee, M.-H. et al. Targeted disruption of p107: functional overlap between p107 and Rb. Genes Dev. 10, 1621-1632 (1996).
90. LeCouter, J. E., Kablar B., Whyte, P. F., Ying, C., Rudnicki, M. A. Strain-dependent embryonic lethality in mice lacking the retinoblastoma-related p130 gene. Development 125, 4669-4679 (1998).
91. LeCouter, J. E. et al. A. Strain-dependent myeloid hyperplasia, growth deficiency, and accelerated cell cycle in mice lacking the pRB-related p107 gene. Mol. Cell. Biol. 18, 7455-7465 (1998).
92. Mulligen, G. J., Weng, J. & Jeeks, T. p130 is dispensable in peripheral T lymphocytes: evidence for functional compensation by p107 and p130. Mol. Cell. Biol. 18, 206-220 (1998).
93. Takahashi, Y., Raymen, J. & Dynlacht, B. Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression. Genes Dev. 14, 804-816 (2000).
94. Wells, J., Boyd, K., Fry, C., Bartley, S. & Fernham, P. Target gene specificity of E2F and pocket protein family members in living cells. Mol. Cell. Biol. 20, 5797-5807 (2000).
95. Bruce, J., Hurford, R., Classon, M., Koh, J. & Dyson, N. Requirements for cell cycle arrest by p16. Mol. Cell. 6. 737-742 (2000).
96. Fajas, L. et al. E2Fs regulate adipocyte differentiation. Dev. Cell. 3, 39-49 (2002).
97. Robenus-Maandeg, E. et al. p107 is a suppressor of retinoblastoma development in pRB-deficient mice. Genes Dev. 12, 1599-1609 (1998). References 88, 89 and 97 initiated analyses of mouse strains that are deficient in Rb, p107 and p130, showing separate and overlapping functions of the proteins in this family.
98. Sage, J. et al. Targeted disruption of the three Rb-related genes leads to loss of G1 control and immortalization. Genes Dev. 14, 3037-3050 (2000).
99. Dannenberg, J.-H., van Rossum, A., Schuijff, L. & te Riele, H. Ablation of the retinoblastoma gene family deregulates G1 control causing immortalization and increased cell turnover under growth-restricting conditions. Genes Dev. 14, 3051-3064 (2000). References 98 and 99 analyse the phenotype of cells deficient in Rb, p107 and p130 isolated from chimeric animals generated using embryonic stem cells that are deficient in all three proteins. These studies indicate that these cells have deregulation of the cell cycle, but it is presently unknown what the contribution of these cells to different tissues is.
100. Vooijs, M., te Riele, H., van der Valk, M. & Berns, A. Tumor formation in mice with somatic inactivation of the retinoblastoma gene in interphotoreceptor retinol binding protein-expressing cells. Oncogene 21, 4635-4645 (2002).
101. Vooijs, M. & Berns, A. Developmental defects and tumor predisposition in Rb mutant mice, Oncogene 18, 5293-5303 (1999).
102. Williams, B. et al. Cooperative tumorigenic effects of germline mutations in Rb and p53. Nature Genet. 7, 480-484 (1994).
103. Windle, J. J. et al. Retinoblastoma in transgenic mice. Nature 343, 665-669 (1990).
104. Saenz Robles, M. T., Symonds, H., Chen, J. & van Dyke, T. Induction versus progression of brain tumor development: differential functions for the pRB and p53-targeting domains of SV40 T antigen. Mol. Cell Biol. 4, 2686-2698 (1994).
105. Howes, K. A. et al. Apoptosis or retinoblastoma: alternative fates of photoreceptors expressing the HPV-16 E7 gene in the presence or absence of p53. Genes Dev. 8, 1300-1310 (1994).
106. Yamasaki, L. et al. Tumor induction and tissue atrophy in mice lacking E2F-1. Cell 85, 537-548 (1996).
107. Field, S. J. et al. E2F-1 functions in mice to promote apoptosis and suppress proliferation. Cell 85, 549-561 (1996). The surprising finding in references 106 and 107 was that ageing mice lacking E2F1 displayed a wide range of tumours.
108. Yamamoto, H. et al. Paradoxical increase in retinoblastoma protein in colorectal carcinomas may protect cells from apoptosis. Clin Cancer Res. 5, 1805-1815 (1999).
109. Elliott, M. J., Dong, Y. B., Yang, H., & McMasters, K. M. E2F-1 upregulates c-Myc and p14ARF and induces apoptosis in colon cancer cells. Clin. Cancer Res. 7, 3590-3597 (2001).
110. Pierce, A. M. et al. E2F1 has both oncogenic and tumor-suppressive properties in a transgenic mouse model. Mol. Cell Biol. 19, 6408-6414 (1999).
111. Pierce, A. M., Fisher, S. M., Conti, C. J. & Johnson, D. G. Deregulated expression of E2F1 induces hyperplasia and cooperates with ras in skin tumor development. Oncogene 12, 1267-1276 (1998).
112. Jiang, Z. & Zacksenhaus, E. Activation of retinoblastoma protein in mammary gland leads to ductal growth suppression, precocious differentiation, and adenocarcinoma. J. Cell Biol. 156, 185-198 (2002). The studies in this paper found a counterintuitive role for a constitutively active (phosphorylation-site mutations) Rb molecule that was found to induce adenocarcinoma in transgenic mice, indicating that too much Rb might prevent apoptotic responses that normally safeguard against tumour formation.
113. Lu, X. & Horvitz, H. R. Iin-35 and Iin-53, two genes that antagonize a C. elegans Ras pathway encode proteins similar to Rb and its binding protein RbAp48. Cell 95, 981-991 (1998).
114. Ceol, C. J. & Horvitz, H. R. dpl-1 DP and efl1 E2F act with lin-35 Rb to antagonize Ras signaling in C. elegans vulval development. Mol Cell, 7, 461-473 (2001).
115. Boxem, M. & van den Heuvel, S. Iin-35 RB and cki-1 Cip/Kip cooperate in developmental regulation of G1 progression in C. elegans. Development 128, 4349-4359 (2001).
116. Boxem, M. & van den Heuvel, S. C. elegans Class B synthetic multivulva genes act in G(1) regulation. Curr. Biol. 12, 906-911 (2002).
117. Duronio, R. J., O'Farrell, P. H., Xie, J.-E., Brook, A. & Dyson, N. The transcription factor E2F is required for S phase during Drosophila embryogenesis. Genes Dev. 9, 1445-1455 (1995).
118. Du, W., Vidal, M., Xie, J.-E. & Dyson, N. RBF, a novel RB-related gene that regulates E2F activity and interacts with cyclin E in Drosophila. Genes Dev. 10, 1206-1218 (1996).
119. Du, W. Suppression of the rbf null mutants by a de2f1 allele that lacks transactivation domain Development 127, 367-379 (2000).
120. Frolov, M. V. et al. Functional antagonism between E2F family members. Genes Dev. 15, 2146-2160 (2001).
121. Myster, D. L., Bonnette, P. C. & Duronio, R. J. A role for the DP subunit of the E2F transcription factor in axis determination during Drosophila oogenesis. Development 121, 3249-3261 (2000).
122. Cayirlioglu, P., Bonnette, P. C., Dickson, M. R. & Duronio, R. J. Drosophila. E2f2 promotes the conversion from genomic DNA replication to gene amplification in ovarian follicle cells. Development 128, 5085-5098 (2001).
123. Stevaux, O., D., D., Frolov, M. V., Taylor-Harding, B., Morris, E. & Dyson, N. Distinct mechanisms of E2F regulation by Drosophila RBF1 and RBF2. EMBO J. 21, 4297-4937 (2002).
124. Neufeld, T. P., de la Cruz, A. F. A., Johnston, L. A. & Edgar, B. A. Coordination of cell growth and division by Drosophila E2F. Cell 93, 1183-1193 (1998).
125. Lee, J.-O., Russo, A. A. & Pavletich, N. P. Structure of the retinoblastoma tumour-suppressor pocket domain bound to a peptide from HPV E7. Nature 391, 859-865 (1998). Describes the crystal structure of the RB pocket bound to E7 and, as such, laid the foundation for many mutational studies of this domain.
126. Dick, F. A., Sailhamer, E. & Dyson, N. J. Mutagenesis of the pRB pocket domain reveals that cell cycle arrest functions are separable from binding to viral oncoproteins. Mol. Cell Biol. 20, 3715-3727 (2000).
127. Dick, F. A. & Dyson, N. J. Three regions of the pRB pocket domain affect its inactivation by human papillomavirus E7 proteins. J. Virol. 76, 6224-6234 (2002).
128. Dahiya, A., Gavin, M. R., Luo, R. X. & Dean, D. C. Role of the LXCXE binding site in Rb function. Cell Biol. 20, 6799-6805 (2000).
129. Chen, T.-T. & Wang, J. Y. J. Establishment of irreversible growth arrest in myogenic differentiation requires the RB LXCXE-binding function. Mol. Cell Biol. 20, 5571-5580 (2000).
130. Knudsen, K. E. et al. RB-dependent S-phase response to DNA damage. Mol. Cell Biol. 20, 7751-7763 (2000).
131. Chestukhin, A., Litovchick, L., Rudich, K. & De Caprio, J. A. Nucleocytoplasmic shuttling of p130: novel regulatory mechanism. Mol. Cell Biol. 22, 453-468 (2002).
132. Chan, H. M., Krstic-Demonacos, M., Smith, L., Demonacos, C. & N. B., L. Acetylation control of the retinoblastoma tumour suppressor protein. Nature Cell Biol. 3, 667-674 (2001).