Enhancement of TGF-β signaling responses by the E3 ubiquitin ligase Arkadia provides tumor suppression in colorectal cancer.

ABSTRACT: TGF-β signaling provides tumor protection against colorectal cancer (CRC). Mechanisms that support its tumor-suppressive properties remain unclear. The ubiquitin ligase Arkadia/RNF111 enhances TGF-β signaling responses by targeting repressors of the pathway for degradation. The corepressors SnoN/Ski, critical substrates of Arkadia, complex with the activated TGF-β signaling effectors Smad2/3 (pSmad2/3) on the promoters of target genes and block their transcription. Arkadia degrades this complex including pSmad2/3 and unblocks the promoter. Here, we report that Arkadia is expressed highly in the mouse colonic epithelium. Heterozygous Akd(+/-) mice are normal but express less Arkadia. This leads to reduced expression of several TGF-β target genes, suggesting that normal levels of Arkadia are

SUBMITTER: Sharma V 

PROVIDER: S-EPMC3194767 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature