Gene Set: PHONG_TNF_RESPONSE_NOT_VIA_P38

Standard name PHONG_TNF_RESPONSE_NOT_VIA_P38
Systematic name M2504
Brief description Genes whose expression changes in Calu-6 cells (lung cancer) by TNF [GeneID=7124] were not affected by p38 inhibitor LY479754.
Full description or abstract p38 mitogen-activated protein kinase (MAPK) is rapidly activated by stresses and is believed to play an important role in the stress response. While Chk1 is known to mediate G(2) DNA damage checkpoint control, p38 was also reported to have an essential function in this checkpoint control. Here, we have investigated further the roles of p38 and Chk1 in the G(2) DNA damage checkpoint in cancer cells. We find that although p38 activation is strongly induced by DNA damage, its activity is not required for the G(2) DNA damage checkpoint. In contrast, Chk1 kinase is responsible for the execution of G(2) DNA damage checkpoint control in p53-deficient cells. The inhibition of p38 activity has no effect on Chk1 activation and gamma-H2AX expression. Global gene expression profiling of cancer cells in response to tumor necrosis factor alpha (TNF-alpha) revealed that p38 plays a strong prosurvival role through the coordinated downregulation of proapoptotic genes and upregulation of prosurvival genes. We show that the inhibition of p38 activity during G(2) DNA damage checkpoint arrest triggers apoptosis in a p53-independent manner with a concurrent decrease in the level of Bcl2 family proteins. Our results suggest that although p38 MAPK is not required for the G(2) DNA damage checkpoint function, it plays an important prosurvival role during the G(2) DNA damage checkpoint response through the upregulation of the Bcl2 family proteins.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 20516219   Authors: Phong MS,Van Horn RD,Li S,Tucker-Kellogg G,Surana U,Ye XS
Exact source Table 2S: p38i LY79754 response=no response
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform AFFY_HG_U133
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Version history 3.1: First introduced

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