Gene Set: HUI_MAPK14_TARGETS_UP

Standard name HUI_MAPK14_TARGETS_UP
Systematic name M1289
Brief description Genes up-regulated in fetal liver (days E13.5 and E15.5) samples from embryo-specific Cre-lox knockout of MAPK14 [GeneID=1432].
Full description or abstract The mitogen-activated protein kinase (MAPK) p38alpha controls inflammatory responses and cell proliferation. Using mice carrying conditional Mapk14 (also known as p38alpha) alleles, we investigated its function in postnatal development and tumorigenesis. When we specifically deleted Mapk14 in the mouse embryo, fetuses developed to term but died shortly after birth, probably owing to lung dysfunction. Fetal hematopoietic cells and embryonic fibroblasts deficient in p38alpha showed increased proliferation resulting from sustained activation of the c-Jun N-terminal kinase (JNK)-c-Jun pathway. Notably, in chemical-induced liver cancer development, mice with liver-specific deletion of Mapk14 showed enhanced hepatocyte proliferation and tumor development that correlated with upregulation of the JNK-c-Jun pathway. Furthermore, inactivation of JNK or c-Jun suppressed the increased proliferation of Mapk14-deficient hepatocytes and tumor cells. These results demonstrate a new mechanism whereby p38alpha negatively regulates cell proliferation by antagonizing the JNK-c-Jun pathway in multiple cell types and in liver cancer development.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17468757   Authors: Hui L,Bakiri L,Mairhorfer A,Schweifer N,Haslinger C,Kenner L,Komnenovic V,Scheuch H,Beug H,Wagner EF
Exact source Table 1S: FC > 0
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Organism Mus musculus
Contributed by Leona Saunders (MSigDB Team)
Source platform Mouse_NCBI_Gene_ID
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Version history 3.1: First introduced

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