The atypical E2F family member E2F7 couples the p53 and RB pathways during cellular senescence

Aksoy, O., Chicas, A., Zeng, T., Zhao, Z., McCurrach, M., Wang, X., Lowe, S. W. (July 2012) The atypical E2F family member E2F7 couples the p53 and RB pathways during cellular senescence. Genes Dev, 26 (14). pp. 1546-57. ISSN 1549-5477 (Electronic)0890-9369 (Linking)

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Abstract

Oncogene-induced senescence is an anti-proliferative stress response program that acts as a fail-safe mechanism to limit oncogenic transformation and is regulated by the retinoblastoma protein (RB) and p53 tumor suppressor pathways. We identify the atypical E2F family member E2F7 as the only E2F transcription factor potently up-regulated during oncogene-induced senescence, a setting where it acts in response to p53 as a direct transcriptional target. Once induced, E2F7 binds and represses a series of E2F target genes and cooperates with RB to efficiently promote cell cycle arrest and limit oncogenic transformation. Disruption of RB triggers a further increase in E2F7, which induces a second cell cycle checkpoint that prevents unconstrained cell division despite aberrant DNA replication. Mechanistically, E2F7 compensates for the loss of RB in repressing mitotic E2F target genes. Together, our results identify a causal role for E2F7 in cellular senescence and uncover a novel link between the RB and p53 pathways.

Item Type:	Paper
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > senescence bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:	Chicas, Agustin Lowe, Scott W. McCurrach, Mila E. Zhao, Zhen Aksoy, Ozlem
Communities:	CSHL labs > Lowe lab School of Biological Sciences > Publications
Depositing User:	Matt Covey
Date:	15 July 2012
Date Deposited:	31 Jan 2013 21:45
Last Modified:	03 Nov 2017 20:05
PMCID:	PMC3404383
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/26889

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