Negative regulation of Odd-skipped related 2 by TGF-beta achieves the induction of cellular migration and the arrest of cell cycle

• Published in: Biochemical and biophysical research communications Vol. 421; no. 4; pp. 696 - 700
• Main Authors: Kawai, Shinji, Amano, Atsuo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.05.2012
• Subjects: Activating Transcription Factor 2 - metabolism; Animals; Base Sequence; Cell Cycle Checkpoints - genetics; Cell Line; Cell Movement - genetics; Cellular migration; Mice; Molecular Sequence Data; Odd-skipped related 2; Promoter; Promoter Regions, Genetic; Smad3 Protein - metabolism; Smad4 Protein - metabolism; Transcription factor; Transcription Factors - genetics; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta - pharmacology; Transforming growth factor-beta; Promoter; Osr2; Cellular migration; CRE; TGF-β; Transforming growth factor-beta; Transcription factor; EMT; Odd-skipped related 2
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2012.04.064

► TGF-β down-regulated Osr2 expression via Smad3/Smad4 and p38/ATF2 signaling molecules. ► Osr2 promoter possessed Smad3/4 and ATF2 binding elements. ► Osr2 reduced the level of cellular migration and stimulated cell-cycle progression. 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.