Oligodendrocyte Transcription Factor 1 (Olig1) Is a Smad Cofactor Involved in Cell Motility Induced by Transforming Growth Factor-β

Transforming growth factor (TGF)-β plays crucial roles in embryonic development and adult tissue homeostasis by eliciting various cellular responses in target cells. TGF-β 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-β-induced cell motility. Knockdown of Olig1 attenuated TGF-β-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-β-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-β-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-β-induced cell motility. These findings may lead to a new strategy for selective regulation of TGF-β-induced cellular responses. Background: To date, the Smad cofactor involved in cell motility induced by transforming growth factor-β (TGF-β) has not been identified. Results: Knockdown of oligodendrocyte transcription factor-1 (Olig1), as well as inhibition of the Olig1-Smad interaction, resulted in attenuation of TGF-β-induced cell motility. Conclusion: Olig1 is involved in TGF-β-induced cell motility. Significance: This study enhances understanding of the regulation of TGF-β-induced cell motility.