RGD Reference Report - TGF-beta repression of Id2 induces apoptosis in gut epithelial cells. - Rat Genome Database

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TGF-beta repression of Id2 induces apoptosis in gut epithelial cells.

Authors: Cao, Y  Liu, X  Zhang, W  Deng, X  Zhang, H  Liu, Y  Chen, L  Thompson, EA  Townsend CM, JR  Ko, TC 
Citation: Cao Y, etal., Oncogene. 2009 Feb 26;28(8):1089-98. doi: 10.1038/onc.2008.456. Epub 2009 Jan 12.
RGD ID: 9686137
Pubmed: PMID:19137015   (View Abstract at PubMed)
PMCID: PMC2943843   (View Article at PubMed Central)
DOI: DOI:10.1038/onc.2008.456   (Journal Full-text)

Transforming growth factor-beta (TGF-beta) regulates epithelial tissue homeostasis by activating processes that control cell cycle arrest, differentiation and apoptosis. Disruption of the TGF-beta signaling pathway often occurs in colorectal cancers. Earlier, we have shown that TGF-beta induces apoptosis through the transcription factor Smad3. Affymetrix oligonucleotide microarrays were used to identify TGF-beta/Smad3 target genes that regulate apoptosis in rat intestinal epithelial cells (RIE-1). We found that TGF-beta repressed the expression of the inhibitor of differentiation (Id) gene family. Knockdown of Id1 and Id2 gene expression induced apoptosis in RIE-1 cells, whereas overexpression of Id2 attenuated TGF-beta-induced apoptosis. TranSignal Protein/DNA arrays were used to identify the hypoxia-inducing factor-1 (HIF-1) as a downstream target of TGF-beta. HIF-1 is a basic helix-loop-helix protein, and overexpression of Id2 blocked HIF-1 activation by TGF-beta. Furthermore, knockdown of HIF-1 blocked TGF-beta-induced apoptosis. Thus, we have identified HIF-1 as a novel mediator downstream of Id2 in the pathway of TGF-beta-induced apoptosis.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Id1Ratnegative regulation of apoptotic process  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Id1  (inhibitor of DNA binding 1)


Additional Information