title: Negative regulation of Odd-skipped related 2 by TGF-beta achieves the induction of cellular migration and the arrest of cell cycle.
abstract: The transcription factor Odd-skipped related 2 (Osr2) functions in craniofacial and limb developments in mammals. We previously found that Osr2 gene expression is regulated by intracellular transcription factors such as Runx2, and C/EBP, whereas it remains unclear if extracellular factors would functionally regulate the Osr2 expression. In this study, we showed that TGF-β down-regulated the Osr2 expression, which is involved in regulation of cellular migration and cell cycle. Furthermore, the down-regulation was found to be mediated by Smad3/Smad4 and p38/ATF2 signaling molecules. The Osr2 promoter was shown to possess Smad3/4 binding element and ATF2 binding element between -647 and -64 of promoter. TGF-β induced cellular migration in C3H10T1/2 cells and arrested cell cycle at G1 phase in NMuMG-Fucci cells. In contrast, the Osr2 reduced the migration and also stimulated the cell-cycle progression. These results suggest that Osr2 is involved in TGF-β regulating cell migration and cell cycle via a Smad3-ATF2 transcriptional complex mediating pathway.
authors.affiliation: Center for Frontier Oral Science, Osaka University Graduate School of Dentistry, Suita-Osaka 565-0871, Japan. skawai@dent.osaka-u.ac.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Kawai
authors.forename: Atsuo
authors.initials: A
authors.lastname: Amano
mesh_terms: D051698:Activating Transcription Factor 2 / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D051900:Smad3 Protein / Q000378:metabolism*; D051901:Smad4 Protein / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; C438618:Osr2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D014157:Transcription Factors; D016212:Transforming Growth Factor beta