title: Oligodendrocyte transcription factor 1 (Olig1) is a Smad cofactor involved in cell motility induced by transforming growth factor-β.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Motizuki
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Isogaya
authors.forename: Kunio
authors.initials: K
authors.lastname: Miyake
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ikushima
authors.forename: Takeo
authors.initials: T
authors.lastname: Kubota
authors.forename: Kohei
authors.initials: K
authors.lastname: Miyazono
authors.forename: Masao
authors.initials: M
authors.lastname: Saitoh
authors.forename: Keiji
authors.initials: K
authors.lastname: Miyazawa
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D019556:COS Cells; D002465:Cell Movement; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014945:Wound Healing
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009419:Nerve Tissue Proteins; D010455:Peptides; D019696:Peptidylprolyl Isomerase; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C405707:OLIG1 protein, human; C494786:Olig1 protein, mouse; C000606846:PIN1 protein, human; C000606850:Pin1 protein, mouse
keywords: Cell Motility; Prolyl Isomerase; Signal Transduction; Smad Transcription Factor; Transforming Growth Factor-β