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.




Biological Process

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Id1Ratnegative regulation of apoptotic process  IMP  RGD 


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