The atypical E2F family member E2F7 couples the p53 and RB pathways during cellular senescence Journal Article
| Authors: | Aksoy, O.; Chicas, A.; Zeng, T.; Zhao, Z.; McCurrach, M.; Wang, X.; Lowe, S. W. |
| Article Title: | The atypical E2F family member E2F7 couples the p53 and RB pathways during cellular senescence |
| 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 upregulated 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. © 2012 by Cold Spring Harbor Laboratory Press. |
| Keywords: | controlled study; human cell; nonhuman; mitosis; animal cell; mouse; animals; mice; mice, knockout; gene targeting; cell division; embryo; cell line; protein p53; cell transformation, neoplastic; oncogene; gene disruption; transcription factor e2f; tumor suppressor protein p53; cell cycle arrest; cell cycle checkpoint; upregulation; protein family; cellular stress response; malignant transformation; retinoblastoma protein; cell aging; checkpoint; rb; compensation; e2f7; p53 target; cell cycle checkpoints; transcription factor e2f7; e2f7 transcription factor |
| Journal Title: | Genes and Development |
| Volume: | 26 |
| Issue: | 14 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2012-07-15 |
| Start Page: | 1546 |
| End Page: | 1557 |
| Language: | English |
| DOI: | 10.1101/gad.196238.112 |
| PROVIDER: | scopus |
| PMCID: | PMC3404383 |
| PUBMED: | 22802529 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 August 2012" - "CODEN: GEDEE" - "Source: Scopus" |
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