Human Gene Set: CHICAS_RB1_TARGETS_SENESCENT


Standard name CHICAS_RB1_TARGETS_SENESCENT
Systematic name M2125
Brief description Genes up-regulated in senescent IMR90 cells (fibroblast) after knockdown of RB1 [GeneID=5925] by RNAi.
Full description or abstract The RB protein family (RB, p107, and p130) has overlapping and compensatory functions in cell-cycle control. However, cancer-associated mutations are almost exclusively found in RB, implying that RB has a nonredundant role in tumor suppression. We demonstrate that RB preferentially associates with E2F target genes involved in DNA replication and is uniquely required to repress these genes during senescence but not other growth states. Consequently, RB loss leads to inappropriate DNA synthesis following a senescence trigger and, together with disruption of a p21-mediated cell-cycle checkpoint, enables extensive proliferation and rampant genomic instability. Our results identify a nonredundant RB effector function that may contribute to tumor suppression and reveal how loss of RB and p53 cooperate to bypass senescence.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 20385362   Authors: Chicas A,Wang X,Zhang C,McCurrach M,Zhao Z,Mert O,Dickins RA,Narita M,Zhang M,Lowe SW
Exact source Table 2S: senescent_shRb_up
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 AFFY_HG_U133
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Version history 3.1: First introduced

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