Unknown,Transcriptomics,Genomics,Proteomics

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Expression data from either growing IMR90 human fibroblasts or senescent IMR90 cells with Ras expression and indicated hairpins


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. To understand the contribution of different genes, especially E2F7 to the expression profile of senescent cells, we infected human IMR90 cells with Ras and different hairpins. The infected population was selected using first with 2 ug/ml puromycin (Sigma) for 2 days, then 100 ug/ml hygromycin B (Roche) for 3 days. RNA was isolated 7 days after the puromycin selection and hybridized to Affymetrix microarrays. We tried to understand the effect of E2F7 in the transcription profile of senescent cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Ozlem Aksoy 

PROVIDER: E-GEOD-40349 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Aksoy Ozlem O   Chicas Agustin A   Zeng Tianying T   Zhao Zhen Z   McCurrach Mila M   Wang Xiaowo X   Lowe Scott W SW  

Genes & development 20120701 14


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 seri  ...[more]

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