HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 3, 1443-1449, January 17, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/3/1443    most recent M210327200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Polager, S. Articles by Ginsberg, D. Search for Related Content PubMed PubMed Citation Articles by Polager, S. Articles by Ginsberg, D. Social Bookmarking                      What's this?

E2F Mediates Sustained G₂ Arrest and Down-regulation of Stathmin and AIM-1 Expression in Response to Genotoxic Stress^*

Shirley Polager and Doron Ginsberg

From the Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel

Exposure of cells to genotoxic agents results in activation of checkpoint pathways leading to cell cycle arrest. These arrest pathways allow repair of damaged DNA before its replication and segregation, thus preventing accumulation of mutations. The tumor suppressor retinoblastoma (RB) is required for the G₁/S checkpoint function. In addition, regulation of the G₂ checkpoint by the tumor suppressor p53 is RB-dependent. However, the molecular mechanism underlying the involvement of RB and its related proteins p107 and p130 in the G₂ checkpoint is not fully understood. We show here that sustained G₂/M arrest induced by the genotoxic agent doxorubicin is E2F-dependent and involves a decrease in expression of two mitotic regulators, Stathmin and AIM-1. Abrogation of E2F function by dominant negative E2F abolishes the doxorubicin-induced down-regulation of Stathmin and AIM-1 and leads to premature exit from G₂. Expression of the E7 papilloma virus protein, which dissociates complexes containing E2F and RB family members, also prevents the down-regulation of these mitotic genes and leads to premature exit from G₂ after genotoxic stress. Furthermore, genotoxic stress increases the levels of nuclear E2F-4 and p130 as well as their in vivo binding to the Stathmin promoter. Thus, functional complexes containing E2F and RB family members appear to be essential for repressing expression of critical mitotic regulators and maintaining the G₂/M checkpoint.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				K. B. Spurgers, D. L. Gold, K. R. Coombes, N. L. Bohnenstiehl, B. Mullins, R. E. Meyn, C. J. Logothetis, and T. J. McDonnell Identification of Cell Cycle Regulatory Genes as Principal Targets of p53-mediated Transcriptional Repression J. Biol. Chem., September 1, 2006; 281(35): 25134 - 25142. [Abstract] [Full Text] [PDF]

				M. W. Jackson, M. K. Agarwal, J. Yang, P. Bruss, T. Uchiumi, M. L. Agarwal, G. R. Stark, and W. R. Taylor, p130/p107/p105Rb-dependent transcriptional repression during DNA-damage-induced cell-cycle exit at G2 J. Cell Sci., May 1, 2005; 118(9): 1821 - 1832. [Abstract] [Full Text] [PDF]

				R. M. Douglas, R. Farahani, P. Morcillo, A. Kanaan, T. Xu, and G. G. Haddad Hypoxia induces major effects on cell cycle kinetics and protein expression in Drosophila melanogaster embryos Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2005; 288(2): R511 - R521. [Abstract] [Full Text] [PDF]