TGF-β repression of Id2 induces apoptosis in gut epithelial cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-02

AUTHORS

Y Cao, X Liu, W Zhang, X Deng, H Zhang, Y Liu, L Chen, E A Thompson, C M Townsend, T C Ko

ABSTRACT

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. More... »

PAGES

1089

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/onc.2008.456

DOI

http://dx.doi.org/10.1038/onc.2008.456

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1031716768

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19137015


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