For the Human gene set with the same name, see RAMJAUN_APOPTOSIS_BY_TGFB1_VIA_SMAD4_DN

Systematic name MM505
Brief description Apoptotic genes dependent on SMAD4 [GeneID=4089] and down-regulated in AML12 cells (hepatocytes) after stimulation with TGFB1 [GeneID=7040].
Full description or abstract Transforming growth factor-beta (TGFbeta)-activated signalling pathways can lead to apoptosis, growth arrest or promotion of malignant behaviour, dependent on cellular context. The molecular mechanisms involved in TGFbeta-induced apoptosis remain controversial; although changes in gene expression are thought to be pivotal to the process, several different candidate apoptotic initiators and mediators have been proposed. Smad4, a critical component of the TGFbeta-induced transcriptional machinery, is shown here to be essential for induction of apoptosis. Gene expression analysis identified the proapoptotic Bcl-2 family members, Bmf and Bim, as induced by TGFbeta, dependent on both Smad4 and p38 function and the generation of reactive oxygen species. TGFbeta-induced Bmf and Bim localize to cellular membranes implicated in apoptosis. Inhibition of the TGFbeta-induced expression of both these proteins together provides significant protection of cells from apoptosis. The TGFbeta-triggered cell death programme thus involves induction of multiple BH3-only proteins during the induction of apoptosis.
Collection M2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16909112   Authors: Ramjaun AR,Tomlinson S,Eddaoudi A,Downward J
Exact source Table 1: TGFb-downregulated genes (smad4 dependent)
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Source species Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
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Version history 2022.1.Mm: First Introduced.

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