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2013 ; 288
(26
): 18911-22
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Oligodendrocyte transcription factor 1 (Olig1) is a Smad cofactor involved in
cell motility induced by transforming growth factor-?
#MMPMID23720758
Motizuki M
; Isogaya K
; Miyake K
; Ikushima H
; Kubota T
; Miyazono K
; Saitoh M
; Miyazawa K
J Biol Chem
2013[Jun]; 288
(26
): 18911-22
PMID23720758
show ga
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.
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