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<MSIGDB BUILD_DATE="Jan 29, 2026" VERSION="2026.1.Hs" NAME="export">
    <GENESET STANDARD_NAME="RAMJAUN_APOPTOSIS_BY_TGFB1_VIA_SMAD4_DN" SYSTEMATIC_NAME="M1151" HISTORICAL_NAMES="" PMID="16909112" AUTHORS="Ramjaun AR,Tomlinson S,Eddaoudi A,Downward J" GEOID="" EXACT_SOURCE="Table 1: TGFb-downregulated genes (smad4 dependent)" GENESET_LISTING_URL="" EXTERNAL_DETAILS_URL="" CHIP="MOUSE_SEQ_ACCESSION" CONTRIBUTOR="Arthur Liberzon" CONTRIBUTOR_ORG="MSigDB Team" DESCRIPTION_BRIEF="Apoptotic genes dependent on SMAD4 [GeneID=4089] and down-regulated in AML12 cells (hepatocytes) after stimulation with TGFB1 [GeneID=7040]." DESCRIPTION_FULL="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." TAGS="" MEMBERS="AF109769,BC003755,BC021490,BG972377,BQ176371,NM_007499,NM_007611,NM_009743,NM_020275,NM_028133" MEMBERS_SYMBOLIZED="ATM,BCL2L1,CASP7,DAPK1,EGLN3,EYA2,MAPK8IP1,SGPP1,TNFRSF10B,TNFRSF21" MEMBERS_EZID="112399,1612,2139,27242,472,598,81537,840,8795,9479" MEMBERS_MAPPING="AF109769,MAPK8IP1,9479|BC003755,EYA2,2139|BC021490,DAPK1,1612|BG972377,TNFRSF21,27242|BQ176371,SGPP1,81537|NM_007499,ATM,472|NM_007611,CASP7,840|NM_009743,BCL2L1,598|NM_020275,TNFRSF10B,8795|NM_028133,EGLN3,112399" FILTERED_BY_SIMILARITY="" FOUNDER_NAMES="" REFINEMENT_DATASETS="" VALIDATION_DATASETS="" CATEGORY_CODE="C2" ORGANISM="Mus musculus" SUB_CATEGORY_CODE="CGP"/>
</MSIGDB>
