PMID: 8956996Dec 1, 1996Paper

The retinoblastoma gene product protects E2F-1 from degradation by the ubiquitin-proteasome pathway

Genes & Development
F HofmannZ M Wang

Abstract

E2F-1 plays a crucial role in the regulation of cell-cycle progression at the G1-S transition. In keeping with the fact that, when overproduced, it is both an oncoprotein and a potent inducer of apoptosis, its transcriptional activity is subject to multiple controls. Among them are binding by the retinoblastoma gene product (pRb), activation by cdk3, and S-phase-dependent down-regulation of DNA-binding capacity by cyclin A-dependent kinase. Here we report that E2F-1 is actively degraded by the ubiquitin-proteasome pathway. Efficient degradation depends on the availability of selected E2F-1 sequences. Unphosphorylated pRb stabilized E2F-1, protecting it from in vivo degradation. pRb-mediated stabilization was not an indirect consequence of G1 arrest, but rather depended on the ability of pRb to interact physically with E2F-1. Thus, in addition to binding E2F-1 and transforming it into a transcriptional repressor, pRb has another function, protection of E2F-1 from efficient degradation during a period when pRb/E2F complex formation is essential to regulating the cell cycle. In addition, there may be a specific mechanism for limiting free E2F-1 levels, failure of which could compromise cell survival and/or homeostasis.

References

Jan 10, 1991·Nature·M GlotzerM W Kirschner
Nov 21, 1995·Proceedings of the National Academy of Sciences of the United States of America·A SchulzeB Henglein
Oct 6, 1995·Cell·C L WardR R Kopito
Apr 1, 1995·Current Opinion in Cell Biology·M Hochstrasser
Jun 1, 1995·Molecular and Cellular Biology·E M HijmansR Bernards
Jun 1, 1995·Molecular and Cellular Biology·R BremnerR A Phillips
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·D G JohnsonJ R Nevins
Feb 1, 1995·Molecular and Cellular Biology·J YaglomD Finley
Feb 1, 1995·Molecular and Cellular Biology·X Q QinW G Kaelin
Feb 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·G XuW Krek
Dec 1, 1994·Current Opinion in Cell Biology·E W Lam, N B La Thangue
Mar 14, 1995·Proceedings of the National Academy of Sciences of the United States of America·C SardetR A Weinberg
Oct 7, 1994·Cell·A Ciechanover
Nov 15, 1994·Genes & Development·D GinsbergD M Livingston
Nov 8, 1994·Proceedings of the National Academy of Sciences of the United States of America·X Q QinP D Adams
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·X Wu, A J Levine
Aug 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·E K FlemingtonW G Kaelin
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·W R SellersW G Kaelin
Dec 19, 1995·Proceedings of the National Academy of Sciences of the United States of America·K OhtaniJ R Nevins
May 17, 1996·Cell·L YamasakiN J Dyson
Apr 1, 1996·Molecular and Cellular Biology·K MobergJ A Lees

❮ Previous
Next ❯

Citations

Aug 14, 1998·Head & Neck·A KhafifP G Sacks
May 20, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·P Lavia, P Jansen-Dürr
Mar 10, 2001·Journal of Cellular Physiology·P R Yew
Dec 3, 1999·Progress in Biophysics and Molecular Biology·K L Craig, M Tyers
Oct 6, 2000·Biochimica Et Biophysica Acta·C A Gilchrist, R T Baker
May 22, 2002·Biochimica Et Biophysica Acta·James DeGregori
Jan 13, 1998·Biochimica Et Biophysica Acta·R Bernards
Feb 5, 2000·Biochimica Et Biophysica Acta·H Müller, K Helin
Sep 11, 1999·The International Journal of Biochemistry & Cell Biology·J S Chen, K Mehta
May 3, 2008·Cell Death and Differentiation·A NemajerovaO Petrenko
Jul 12, 2011·Oncogene·M VerhaegenM S Soengas
May 13, 1999·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·S Hayashi, M Yamaguchi
Sep 26, 2008·Molecular Biology of the Cell·Isabella ManniGiulia Piaggio
Jul 21, 2009·Cardiovascular Research·Pasquale FasanaroFabio Martelli
Feb 17, 2000·The EMBO Journal·M A Martínez-BalbásT Kouzarides
Feb 26, 2003·Genes & Development·Karen CichowskiTyler Jacks
Dec 17, 2004·Genes & Development·Marshall UristCarol Prives
Sep 29, 1999·Genes & Development·J D SingerJ M Roberts
Feb 1, 2005·Journal of Virology·Joel E SchaleyPatrick Hearing
Nov 10, 2007·Molecular and Cellular Biology·Alessandra MagentaFabio Martelli
Feb 25, 2000·Molecular and Cellular Biology·O Loughran, N B La Thangue
Feb 7, 2001·Molecular and Cellular Biology·S GaubatzD M Livingston
Apr 10, 2002·Molecular and Cellular Biology·Hong YangDavid M Livingston
Aug 15, 2003·Molecular and Cellular Biology·Apollina Goel, Ralf Janknecht
Sep 2, 2005·Molecular and Cellular Biology·Abhishek DattaPradip Raychaudhuri
Oct 6, 1998·Annual Review of Biochemistry·A Hershko, A Ciechanover
Jan 14, 2010·Cancer Research·Adriana De SierviKevin Gardner
Apr 4, 2003·Biological Chemistry·Doris GerullisDetmar Beyersmann

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis