| First Author | Tintignac LA | Year | 2004 |
| Journal | Mol Cell Biol | Volume | 24 |
| Issue | 4 | Pages | 1809-21 |
| PubMed ID | 14749395 | Mgi Jnum | J:87677 |
| Mgi Id | MGI:3027412 | Doi | 10.1128/MCB.24.4.1809-1821.2004 |
| Citation | Tintignac LA, et al. (2004) Mutant MyoD lacking Cdc2 phosphorylation sites delays M-phase entry. Mol Cell Biol 24(4):1809-21 |
| abstractText | The transcription factors MyoD and Myf-5 control myoblast identity and differentiation. MyoD and Myf-5 manifest opposite cell cycle-specific expression patterns. Here, we provide evidence that MyoD plays a pivotal role at the G(2)/M transition by controlling the expression of p21(Waf1/Cip1) (p21), which is believed to regulate cyclin B-Cdc2 kinase activity in G(2). In growing myoblasts, MyoD reaccumulates during G(2) concomitantly with p21 before entry into mitosis; MyoD is phosphorylated on Ser5 and Ser200 by cyclin B-Cdc2, resulting in a decrease of its stability and down-regulation of both MyoD and p21. Inducible expression of a nonphosphorylable MyoD A5/A200 enhances the MyoD interaction with the coactivator P/CAF, thereby stimulating the transcriptional activation of a luciferase reporter gene placed under the control of the p21 promoter. MyoD A5/A200 causes sustained p21 expression, which inhibits cyclin B-Cdc2 kinase activity in G(2) and delays M-phase entry. This G(2) arrest is not observed in p21(-/-) cells. These results show that in cycling cells MyoD functions as a transcriptional activator of p21 and that MyoD phosphorylation is required for G(2)/M transition. |
