pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes.
10.1101/gad.11.11.1447
Crossref journal-article
Cold Spring Harbor Laboratory
Genes & Development (246)
Abstract

The activity of the E2F transcription factor is controlled by physical association with the retinoblastoma protein (pRB) and two related proteins, p107 and p130. The pRB family members are thought to control different aspects of E2F activity, but it has been unclear what the respective functions of these proteins might be. To dissect the specific functions of pRB, p107, and p130 we have investigated how the expression of E2F-regulated genes is changed in cultures of primary cells lacking each of these family members. Whereas no changes were found in the expression of E2F-target genes in cells lacking either p107 or p130, deregulated expression of E2F targets was seen in cells lacking pRB and in cells lacking both p107 and p130. Surprisingly, the genes that were disregulated in these two settings were completely different. These findings show that pRB and p107/p130 indeed provide different functions in E2F regulation and identify target genes that are dependent on pRB family proteins for their normal expression.

Bibliography

Hurford, R. K., Cobrinik, D., Lee, M. H., & Dyson, N. (1997). pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes. Genes & Development, 11(11), 1447–1463.

Authors 4
  1. R K Hurford (first)
  2. D Cobrinik (additional)
  3. M H Lee (additional)
  4. N Dyson (additional)
References 85 Referenced 345
  1. {'key': '2021111418451032000_11.11.1447.1', 'first-page': '79', 'article-title': 'The cellular effects of E2F overexpression.', 'volume': '208', 'year': '1996', 'journal-title': 'Curr. Top. Microbiol. Immunol.'} / Curr. Top. Microbiol. Immunol. / The cellular effects of E2F overexpression. (1996)
  2. 10.1073/pnas.92.12.5436
  3. 10.1101/gad.8.22.2680
  4. 10.1128/MCB.16.7.3401 / Mol. Cell. Biol. / Cell cycle regulation of the murine cyclin E gene depends on an E2F binding site in the promoter. (1996)
  5. 10.1038/355176a0
  6. {'key': '2021111418451032000_11.11.1447.6', 'first-page': '79', 'article-title': 'The retinoblastoma protein as a fundamental mediator of growth and differentiation signals.', 'volume': '5', 'year': '1995', 'journal-title': 'Crit. Rev. Eukaryotic Gene Expression'} / Crit. Rev. Eukaryotic Gene Expression / The retinoblastoma protein as a fundamental mediator of growth and differentiation signals. (1995)
  7. {'key': '2021111418451032000_11.11.1447.7', 'first-page': '3975', 'article-title': 'Cell cycle analysis of E2F in primary human T cells reveals novel E2F complexes and biochemically distinct forms of free E2F.', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Cell cycle analysis of E2F in primary human T cells reveals novel E2F complexes and biochemically distinct forms of free E2F. (1993)
  8. 10.1038/359328a0
  9. {'key': '2021111418451032000_11.11.1447.9', 'first-page': '31', 'article-title': 'Regulatory interactions among E2Fs and cell cycle control proteins.', 'volume': '208', 'year': '1996', 'journal-title': 'Curr. Top. Microbiol. Immunol.'} / Curr. Top. Microbiol. Immunol. / Regulatory interactions among E2Fs and cell cycle control proteins. (1996)
  10. 10.1101/gad.7.12a.2392
  11. 10.1101/gad.10.13.1633
  12. {'key': '2021111418451032000_11.11.1447.12', 'first-page': '909', 'article-title': 'Characterization of transcription factor E2F complexes during muscle and neuronal differentiation.', 'volume': '11', 'year': '1995', 'journal-title': 'Oncogene'} / Oncogene / Characterization of transcription factor E2F complexes during muscle and neuronal differentiation. (1995)
  13. {'key': '2021111418451032000_11.11.1447.13', 'first-page': '6314', 'article-title': 'A genetic analysis of the E2F1 gene distinguishes regulation by Rb, p107, and adenovirus E4.', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / A genetic analysis of the E2F1 gene distinguishes regulation by Rb, p107, and adenovirus E4. (1993)
  14. 10.1002/j.1460-2075.1992.tb05231.x / EMBO J. / Cell cycle regulation of the human cdc2 gene. (1992)
  15. 10.1128/MCB.15.8.4215 / Mol. Cell. Biol. / Cellular targets for activation by the E2F1 transcription factor include DNA synthesis and G1/S regulatory genes. (1995)
  16. 10.1016/0092-8674(92)90215-X
  17. Dyson, N.J. 1991. Immobilization of nucleic acids and hybridization analysis. In Essential molecular biology: A practical approach (ed. T.A. Brown), pp. 111–156. IRL Press at Oxford University Press, Oxford, UK.
  18. 10.1128/jvi.67.12.7641-7647.1993 / J. Virol. / Analysis of p107-associated proteins: p107 associates with a form of E2F that differs from pRB-associated E2F-1. (1993)
  19. Famham, P.J. 1996. Transcriptional control of cell growth: The E2F family. Springer Verlag, New York, N.Y. (10.1007/978-3-642-79910-5)
  20. 10.1128/MCB.17.4.1966 / Mol. Cell. Biol. / Position-dependent transcriptional regulation of the murine dihydrofolate reductase promoter by the E2F transactivation domain. (1997)
  21. {'key': '2021111418451032000_11.11.1447.21', 'first-page': '1173', 'article-title': 'Regulation of cyclin E transcription by E2Fs and retinoblastoma protein.', 'volume': '12', 'year': '1996', 'journal-title': 'Oncogene'} / Oncogene / Regulation of cyclin E transcription by E2Fs and retinoblastoma protein. (1996)
  22. {'key': '2021111418451032000_11.11.1447.22', 'first-page': '467', 'article-title': 'Characterization of the human RB1 promoter and of elements involved in transcriptional regulation.', 'volume': '5', 'year': '1994', 'journal-title': 'Cell Growth Differ.'} / Cell Growth Differ. / Characterization of the human RB1 promoter and of elements involved in transcriptional regulation. (1994)
  23. 10.1101/gad.8.22.2665
  24. {'key': '2021111418451032000_11.11.1447.24', 'first-page': '3431', 'article-title': 'Transcriptional repression of the E2-containing promoters EIIaE, c-myc, and RB1 by the product of the RB1 gene.', 'volume': '12', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Transcriptional repression of the E2-containing promoters EIIaE, c-myc, and RB1 by the product of the RB1 gene. (1992)
  25. 10.1002/(SICI)1097-0142(19960801)78:3<558::AID-CNCR26>3.0.CO;2-X
  26. Harlow, E. and D. Lane. 1988. Antibodies: A laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
  27. 10.1101/gad.10.23.2960
  28. 10.1128/MCB.16.5.2402 / Mol. Cell. Biol. / Altered cell cycle kinetics, gene expression, and G1 restriction point regulation in Rb-deficient fibroblasts. (1996)
  29. 10.1073/pnas.93.21.11510
  30. 10.1073/pnas.86.10.3594
  31. 10.1128/MCB.15.6.3082 / Mol. Cell. Biol. / E2F-5, a new E2F family member that interacts with p130 in vivo. (1995)
  32. 10.1101/gad.10.23.2949
  33. 10.1101/gad.8.13.1526
  34. 10.1128/MCB.16.7.3789 / Mol. Cell. Biol. / Cyclin A expression is under negative transcriptional control during the cell cycle. (1996)
  35. 10.1038/359295a0
  36. 10.1038/365349a0
  37. 10.1101/gad.8.13.1514
  38. 10.1016/0955-0674(92)90025-8
  39. 10.1128/MCB.16.4.1659 / Mol. Cell. Biol. / Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F. (1996)
  40. 10.1006/geno.1995.1184
  41. 10.1093/nar/19.14.3998
  42. 10.1002/j.1460-2075.1993.tb05932.x / EMBO J. / An E2F-binding site mediates cell-cycle regulated repression of mouse B-myb transcription. (1993)
  43. 10.1002/j.1460-2075.1994.tb06330.x / EMBO J. / HPV16 E7 oncoprotein deregulates B-myb expression: correlation with targeting of p107/E2F complexes. (1994)
  44. 10.1038/359288a0
  45. 10.1101/gad.8.17.2008
  46. {'key': '2021111418451032000_11.11.1447.46', 'first-page': '95', 'article-title': 'Regulation of cyclin D1, DNA topoisomerase I, and proliferating cell nuclear antigen promoters during the cell cycle.', 'volume': '4', 'year': '1995', 'journal-title': 'Gene Expr.'} / Gene Expr. / Regulation of cyclin D1, DNA topoisomerase I, and proliferating cell nuclear antigen promoters during the cell cycle. (1995)
  47. 10.1101/gad.10.13.1621
  48. 10.1128/MCB.13.12.7813
  49. 10.1128/MCB.15.5.2600 / Mol. Cell. Biol. / Cyclin D1 is dispensable for G1 control in retinoblastoma gene-deficient cells independently of cdk4 activity. (1995)
  50. 10.1128/MCB.16.3.1047 / Mol. Cell. Biol. / Deregulated expression of E2F family members induces S-phase entry and overcomes p16INK4A-mediated growth suppression. (1996)
  51. {'key': '2021111418451032000_11.11.1447.51', 'first-page': '1054', 'article-title': 'The HIP1 binding site is required for growth regulation of the dihydrofolate reductase gene promoter.', 'volume': '12', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / The HIP1 binding site is required for growth regulation of the dihydrofolate reductase gene promoter. (1992)
  52. 10.1128/MCB.16.4.1436 / Mol. Cell. Biol. / E2F-4 switches from p130 to p107 and pRB in response to cell cycle reentry. (1996)
  53. {'key': '2021111418451032000_11.11.1447.53', 'first-page': '4660', 'article-title': 'Transcription of the E2F-1 gene is rendered cell cycle dependent by E2F DNA-binding sites within its promoter', 'volume': '15', 'year': '1994', 'journal-title': 'Mol. Cell. Biol. 1995.'} / Mol. Cell. Biol. 1995. / Transcription of the E2F-1 gene is rendered cell cycle dependent by E2F DNA-binding sites within its promoter (1994)
  54. 10.1128/jvi.67.4.1765-1771.1993 / J. Virol. / A binding site for transcription factor E2F is a target for trans activation of murine thymidine kinase by polyomavirus large T antigen and plays an important role in growth regulation of the gene. (1993)
  55. 10.1073/pnas.92.26.12146
  56. {'key': '2021111418451032000_11.11.1447.56', 'first-page': '1703', 'article-title': 'A silencer element in the retinoblastoma tumor-suppressor gene.', 'volume': '9', 'year': '1994', 'journal-title': 'Oncogene'} / Oncogene / A silencer element in the retinoblastoma tumor-suppressor gene. (1994)
  57. 10.1126/science.8384376
  58. {'key': '2021111418451032000_11.11.1447.58', 'first-page': '2081', 'article-title': 'Human DNA polymerase alpha gene: sequences controlling expression in cycling and serum-stimulated cells.', 'volume': '11', 'year': '1991', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Human DNA polymerase alpha gene: sequences controlling expression in cycling and serum-stimulated cells. (1991)
  59. {'key': '2021111418451032000_11.11.1447.59', 'first-page': '2125', 'article-title': 'An E2F binding sequence negatively regulates the response of the insulin-like growth factor 1 (IGF-I) promoter to simian virus 40T antigen and to serum.', 'volume': '9', 'year': '1994', 'journal-title': 'Oncogene'} / Oncogene / An E2F binding sequence negatively regulates the response of the insulin-like growth factor 1 (IGF-I) promoter to simian virus 40T antigen and to serum. (1994)
  60. {'key': '2021111418451032000_11.11.1447.60', 'first-page': '4032', 'article-title': 'Repression of cyclin D1: A novel function of MYC.', 'volume': '14', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Repression of cyclin D1: A novel function of MYC. (1994)
  61. {'key': '2021111418451032000_11.11.1447.61', 'first-page': '5363', 'article-title': 'Biological function of the retinoblastoma protein requires distinct domains for hyperphosphorylation and transcription factor binding.', 'volume': '12', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Biological function of the retinoblastoma protein requires distinct domains for hyperphosphorylation and transcription factor binding. (1992)
  62. {'key': '2021111418451032000_11.11.1447.62', 'first-page': '1669', 'article-title': 'Acceleration of the G1/S phase transition by expression of cyclins D1 and E with an inducible system.', 'volume': '14', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Acceleration of the G1/S phase transition by expression of cyclins D1 and E with an inducible system. (1994)
  63. 10.1016/S0955-0674(96)80004-4
  64. 10.1126/science.8197461
  65. 10.1073/pnas.92.24.11264
  66. 10.1128/MCB.16.9.4632 / Mol. Cell. Biol. / Anchorage-dependent transcription of the cyclin A gene. (1996)
  67. 10.1002/j.1460-2075.1993.tb05742.x / EMBO J. / Interactions of the p107 and Rb proteins with E2F during the cell proliferation response. (1993)
  68. {'key': '2021111418451032000_11.11.1447.68', 'first-page': '299', 'article-title': 'The transcription factor E2F-1 mediates the autoregulation of RB gene expression.', 'volume': '14', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / The transcription factor E2F-1 mediates the autoregulation of RB gene expression. (1994)
  69. 10.1126/science.274.5293.1672
  70. 10.1016/0092-8674(92)90214-W
  71. {'key': '2021111418451032000_11.11.1447.71', 'first-page': '1', 'article-title': 'Introduction to the E2F family: Protein structure and gene regulation.', 'volume': '208', 'year': '1996', 'journal-title': 'Curr. Top. Microbiol. Immunol.'} / Curr. Top. Microbiol. Immunol. / Introduction to the E2F family: Protein structure and gene regulation. (1996)
  72. {'key': '2021111418451032000_11.11.1447.72', 'first-page': '7201', 'article-title': 'A protein synthesis-dependent increase in E2F1 mRNA correlates with growth regulation of the dihydrofolate reductase promoter', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol. 1993.'} / Mol. Cell. Biol. 1993. / A protein synthesis-dependent increase in E2F1 mRNA correlates with growth regulation of the dihydrofolate reductase promoter (1993)
  73. 10.1128/MCB.16.12.6965 / Mol. Cell. Biol. / The accumulation of an E2F-p130 transcriptional repressor distinguishes a G0 cell state from a G1 phase state. (1996)
  74. Tabor, S. and K. Struhl. 1994. DNA-dependent DNA polymerases. In Current protocols in molecular biology (ed. F.M. Ausubel, R. Brent, R.E. Kingston, D.D. Moore, J.G. Seidman, J.A. Smith, and K. Struhl], pp. 3.5.1–3.5.15. Wiley/Greene, New York, NY.
  75. 10.1101/gad.3.4.527
  76. 10.1128/MCB.15.12.6901 / Mol. Cell. Biol / In vivo structure of the human cdc2 promoter: Release of a p130-E2F6-4 complex from sequences immediately upstream of the transcription initiation site coincides with induction of cdc2 expression. (1995)
  77. 10.1016/0092-8674(95)90385-2
  78. 10.1038/358259a0
  79. 10.1038/375812a0
  80. 10.1101/gad.9.1.31
  81. {'key': '2021111418451032000_11.11.1447.81', 'first-page': '995', 'article-title': 'Inducible acceleration of G1 progression through tetracycline-regulated expression of human cyclin E.', 'volume': '9', 'year': '1994', 'journal-title': 'Oncogene'} / Oncogene / Inducible acceleration of G1 progression through tetracycline-regulated expression of human cyclin E. (1994)
  82. 10.1002/j.1460-2075.1987.tb02471.x / EMBO J. / Promoter interaction of the E1A-inducible factor E2F and its potential role in the formation of a multi-component complex. (1987)
  83. 10.1101/gad.7.7a.1111
  84. 10.1128/MCB.15.7.3552 / Mol. Cell. Biol. / Differential roles of two tandem E2F sites in repression of the human p107 promoter by retinoblastoma and p107 proteins. (1995)
  85. {'key': '2021111418451032000_11.11.1447.85', 'first-page': '4514', 'article-title': 'Cell cycle regulation of the cyclin A, cdc25C and cdc2 genes is based on a common mechanism of transcriptional repression.', 'volume': '14', 'year': '1996', 'journal-title': 'EMBO J.'} / EMBO J. / Cell cycle regulation of the cyclin A, cdc25C and cdc2 genes is based on a common mechanism of transcriptional repression. (1996)
Dates
Type When
Created 18 years, 3 months ago (June 5, 2007, 5:15 p.m.)
Deposited 3 years, 9 months ago (Nov. 14, 2021, 10:04 p.m.)
Indexed 2 months, 1 week ago (June 25, 2025, 7:49 p.m.)
Issued 28 years, 3 months ago (June 1, 1997)
Published 28 years, 3 months ago (June 1, 1997)
Published Online 28 years, 3 months ago (June 1, 1997)
Published Print 28 years, 3 months ago (June 1, 1997)
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@article{Hurford_1997, title={pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes.}, volume={11}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.11.11.1447}, DOI={10.1101/gad.11.11.1447}, number={11}, journal={Genes &amp; Development}, publisher={Cold Spring Harbor Laboratory}, author={Hurford, R K and Cobrinik, D and Lee, M H and Dyson, N}, year={1997}, month=jun, pages={1447–1463} }