| First Author | Motizuki M | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 26 | Pages | 18911-22 |
| PubMed ID | 23720758 | Mgi Jnum | J:199649 |
| Mgi Id | MGI:5504311 | Doi | 10.1074/jbc.M113.480996 |
| Citation | Motizuki M, et al. (2013) Oligodendrocyte transcription factor 1 (Olig1) is a Smad cofactor involved in cell motility induced by transforming growth factor-beta. J Biol Chem 288(26):18911-22 |
| abstractText | Transforming growth factor (TGF)-beta plays crucial roles in embryonic development and adult tissue homeostasis by eliciting various cellular responses in target cells. TGF-beta 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-beta-induced cell motility. Knockdown of Olig1 attenuated TGF-beta-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-beta-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-beta-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-beta-induced cell motility. These findings may lead to a new strategy for selective regulation of TGF-beta-induced cellular responses. |
