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Genes Dev. 2012 Jul 15;26(14):1546-57. doi: 10.1101/gad.196238.112.

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

Author information

1
Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.

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.

PMID:
22802529
PMCID:
PMC3404383
DOI:
10.1101/gad.196238.112
[Indexed for MEDLINE]
Free PMC Article

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