This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Saavedra, H. I. Articles by Leone, G. Search for Related Content PubMed PubMed Citation Articles by Saavedra, H. I. Articles by Leone, G.

Specificity of E2F1, E2F2, and E2F3 in Mediating Phenotypes Induced by Loss of Rb¹

Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics and Departments of Molecular Genetics [H. I. S., L. W., A. d. B., C. T., M. W., G. L.], Veterinary Biosciences [A. d. B., T. J. R.], and Pediatrics [M. L. R.], and Division of Molecular and Human Genetics, Children’s Research Institute [M. L. R.], The Ohio State University, Columbus, Ohio 43210

The Rb/E2F pathway plays a critical role in the control of cellular proliferation. Here, we report that E2F1, E2F2, and E2F3 make major individual contributions toward the in vivo phenotypic consequences of Rb deficiency. In the developing lens of Rb^-/- embryos, loss of E2F1, E2F2, or E2F3 reduces the unscheduled proliferation of fiber cells, with the loss of E2F3 having the most pronounced effect. In Rb-deficient retinas, all three E2Fs contribute equally to the ectopic proliferation of postmitotic neuronal cells. In contrast, E2F1 is unique in mediating apoptosis in both Rb^-/- lenses and retinas. In the central nervous system, loss of E2F1 or E2F3 can almost completely eliminate the ectopic DNA replication and apoptosis observed in Rb^-/- embryos, and loss of E2F2 partially reduces the unscheduled DNA replication and has no effect on apoptosis. These results provide clear evidence for functional specificity among E2Fs in the control of Rb-dependent proliferation and apoptosis in a tissue-specific manner.

This article has been cited by other articles:

				V. T. Mihaylova, A. M. Green, M. Khurgel, O. J. Semmes, and G. M. Kupfer Human T-Cell Leukemia Virus I Tax Protein Sensitizes p53-Mutant Cells to DNA Damage Cancer Res., June 15, 2008; 68(12): 4843 - 4852. [Abstract] [Full Text] [PDF]

				E. Angelis, A. Garcia, S. S. Chan, K. Schenke-Layland, S. Ren, S. J. Goodfellow, M. C. Jordan, K. P. Roos, R. J. White, and W. R. MacLellan A Cyclin D2-Rb Pathway Regulates Cardiac Myocyte Size and RNA Polymerase III After Biomechanical Stress in Adult Myocardium Circ. Res., May 23, 2008; 102(10): 1222 - 1229. [Abstract] [Full Text] [PDF]

				A. Dirlam, B. T. Spike, and K. F. Macleod Deregulated E2f-2 Underlies Cell Cycle and Maturation Defects in Retinoblastoma Null Erythroblasts Mol. Cell. Biol., December 15, 2007; 27(24): 8713 - 8728. [Abstract] [Full Text] [PDF]

				P. H. Giangrande, J. Zhang, A. Tanner, A. D. Eckhart, R. E. Rempel, E. R. Andrechek, J. M. Layzer, J. R. Keys, P.-O. Hagen, J. R. Nevins, et al. Distinct roles of E2F proteins in vascular smooth muscle cell proliferation and intimal hyperplasia PNAS, August 7, 2007; 104(32): 12988 - 12993. [Abstract] [Full Text] [PDF]

				K. A. McClellan, V. A. Ruzhynsky, D. N. Douda, J. L. Vanderluit, K. L. Ferguson, D. Chen, R. Bremner, D. S. Park, G. Leone, and R. S. Slack Unique Requirement for Rb/E2F3 in Neuronal Migration: Evidence for Cell Cycle-Independent Functions Mol. Cell. Biol., July 1, 2007; 27(13): 4825 - 4843. [Abstract] [Full Text] [PDF]

				P. Ahuja, P. Sdek, and W. R. MacLellan Cardiac Myocyte Cell Cycle Control in Development, Disease, and Regeneration Physiol Rev, April 1, 2007; 87(2): 521 - 544. [Abstract] [Full Text] [PDF]

				T. Parisi, T. L. Yuan, A. M. Faust, A. M. Caron, R. Bronson, and J. A. Lees Selective Requirements for E2f3 in the Development and Tumorigenicity of Rb-Deficient Chimeric Tissues Mol. Cell. Biol., March 15, 2007; 27(6): 2283 - 2293. [Abstract] [Full Text] [PDF]

				P. L. Wenzel, L. Wu, A. de Bruin, J.-L. Chong, W.-Y. Chen, G. Dureska, E. Sites, T. Pan, A. Sharma, K. Huang, et al. Rb is critical in a mammalian tissue stem cell population Genes & Dev., January 1, 2007; 21(1): 85 - 97. [Abstract] [Full Text] [PDF]

				M. Gu, R. P. Singh, S. Dhanalakshmi, S. Mohan, and R. Agarwal Differential effect of silibinin on E2F transcription factors and associated biological events in chronically UVB-exposed skin versus tumors in SKH-1 hairless mice. Mol. Cancer Ther., August 1, 2006; 5(8): 2121 - 2129. [Abstract] [Full Text] [PDF]

				G. Qin, R. Kishore, C. M. Dolan, M. Silver, A. Wecker, C. N. Luedemann, T. Thorne, A. Hanley, C. Curry, L. Heyd, et al. Cell cycle regulator E2F1 modulates angiogenesis via p53-dependent transcriptional control of VEGF PNAS, July 18, 2006; 103(29): 11015 - 11020. [Abstract] [Full Text] [PDF]

				T. C. Hallstrom and J. R. Nevins Jab1 is a specificity factor for E2F1-induced apoptosis Genes & Dev., March 1, 2006; 20(5): 613 - 623. [Abstract] [Full Text] [PDF]

				H. Sun, Y. Chang, B. Schweers, M. A. Dyer, X. Zhang, S. W. Hayward, and D. W. Goodrich An E2F Binding-Deficient Rb1 Protein Partially Rescues Developmental Defects Associated with Rb1 Nullizygosity Mol. Cell. Biol., February 15, 2006; 26(4): 1527 - 1537. [Abstract] [Full Text] [PDF]

				C. Takahashi, B. Contreras, R. T. Bronson, M. Loda, and M. E. Ewen Genetic Interaction between Rb and K-ras in the Control of Differentiation and Tumor Suppression Mol. Cell. Biol., December 1, 2004; 24(23): 10406 - 10415. [Abstract] [Full Text] [PDF]

				U. Ziebold, E. Y. Lee, R. T. Bronson, and J. A. Lees E2F3 Loss Has Opposing Effects on Different pRB-Deficient Tumors, Resulting in Suppression of Pituitary Tumors but Metastasis of Medullary Thyroid Carcinomas Mol. Cell. Biol., September 15, 2003; 23(18): 6542 - 6552. [Abstract] [Full Text] [PDF]

				F. X. Li, J. W. Zhu, C. J. Hogan, and J. DeGregori Defective Gene Expression, S Phase Progression, and Maturation during Hematopoiesis in E2F1/E2F2 Mutant Mice Mol. Cell. Biol., May 15, 2003; 23(10): 3607 - 3622. [Abstract] [Full Text] [PDF]

				S. D. MUNDLE and G. SABERWAL Evolving intricacies and implications of E2F1 regulation FASEB J, April 1, 2003; 17(6): 569 - 574. [Abstract] [Full Text] [PDF]