| First Author | Kobayashi N | Year | 2007 |
| Journal | Genes Cells | Volume | 12 |
| Issue | 3 | Pages | 375-85 |
| PubMed ID | 17352741 | Mgi Jnum | J:127114 |
| Mgi Id | MGI:3762994 | Doi | 10.1111/j.1365-2443.2007.01052.x |
| Citation | Kobayashi N, et al. (2007) c-Ski activates MyoD in the nucleus of myoblastic cells through suppression of histone deacetylases. Genes Cells 12(3):375-85 |
| abstractText | c-Ski, originally identified as an oncogene product, induces myogenic differentiation in nonmyogenic fibroblasts through transcriptional activation of muscle regulatory factors. Although c-Ski does not bind to DNA directly, it binds to DNA through interaction with Smad proteins and regulates signaling activities of transforming growth factor-beta (TGF-beta). In the present study, we show that c-Ski activates the myogenin promoter independently of regulation of endogenous TGF-beta signaling. Expression of myogenin is regulated by a transcription factor complex containing proteins of the MyoD family and the myocyte enhancer factor 2 (MEF2) family. c-Ski acts on the MyoD-MEF2 complex and modulates the activity of MyoD in myogenin promoter regulation. Interestingly, histone deacetylase (HDAC) inhibitors up-regulated basal activity of transcription from a MyoD-responsive reporter, although c-Ski failed to further augment this transcription in the presence of HDAC inhibitors. c-Ski is observed both in the cytoplasm and in the nucleus, but its nuclear localization is required for myogenic differentiation. We conclude that c-Ski induces myogenic differentiation through acting on MyoD and inhibiting HDAC activity in the nucleus of myogenic cells. |
