Human Gene Set: LIU_TOPBP1_TARGETS


Standard name LIU_TOPBP1_TARGETS
Systematic name M2382
Brief description Genes up-regulated in U2OS cells (osteosarcoma) upon knockdown of TOPBP1 [GeneID=11073].
Full description or abstract Proper control of the G(1)/S checkpoint is essential for normal proliferation. The activity of p53 must be kept at a very low level under unstressed conditions to allow growth. Here we provide evidence supporting a crucial role for TopBP1 in actively repressing p53. Depletion of TopBP1 upregulates p53 target genes involved in cell cycle arrest and apoptosis and enhances DNA damage-induced apoptosis. The regulation is mediated by an interaction between the seventh and eighth BRCT domains of TopBP1 and the DNA-binding domain of p53, leading to inhibition of p53 promoter binding activity. Importantly, TopBP1 overexpression is found in 46 of 79 primary breast cancer tissues and is associated with high tumor grade and shorter patient survival time. Overexpression of TopBP1 to a level comparable to that seen in breast tumors leads to inhibition of p53 target gene expression and DNA damage-induced apoptosis and G(1) arrest. Thus, a physiological level of TopBP1 is essential for normal G(1)/S transition, but a pathological level of TopBP1 in cancer may perturb p53 function and contribute to an aggressive tumor behavior.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 19289498   Authors: Liu K,Bellam N,Lin HY,Wang B,Stockard CR,Grizzle WE,Lin WC
Exact source Table 1S
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 HUMAN_SEQ_ACCESSION
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