Oligodendrocyte transcription factor 1 (Olig1) is a Smad cofactor involved in cell motility induced by transforming growth factor-?.

ABSTRACT: Transforming growth factor (TGF)-? plays crucial roles in embryonic development and adult tissue homeostasis by eliciting various cellular responses in target cells. TGF-? signaling is principally mediated through receptor-activated Smad proteins, which regulate expression of target genes in cooperation with other DNA-binding transcription factors (Smad cofactors). In this study, we found that the basic helix-loop-helix transcription factor Olig1 is a Smad cofactor involved in TGF-?-induced cell motility. Knockdown of Olig1 attenuated TGF-?-induced cell motility in chamber migration and wound healing assays. In contrast, Olig1 knockdown had no effect on bone morphogenetic protein-induced cell motility, TGF-?-induced cytostasis, or epithelial-mesenchymal transition. Furthermore, we observed that cooperation of Smad2/3 with Olig1 is regulated by a peptidyl-prolyl cis/trans-isomerase, Pin1. TGF-?-induced cell motility, induction of Olig1-regulated genes, and physical interaction between Smad2/3 and Olig1 were all inhibited after knockdown of Pin1, indicating a novel mode of regulation of Smad signaling. We also found that Olig1 interacts with the L3 loop of Smad3. Using a synthetic peptide corresponding to the L3 loop of Smad3, we succeeded in selectively inhibiting TGF-?-induced cell motility. These findings may lead to a new strategy for selective regulation of TGF-?-induced cellular responses.

SUBMITTER: Motizuki M 

PROVIDER: S-EPMC3696667 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature