Résumé
Regulation of the MyoD expression level, a skeletal muscle specific transcription factor, is dispensable to cell cycle arrest and activation of muscle gene expression required for myogenic differentiation program. In normal myoblasts, MyoD is expressed in G1 phase and end-G2 phase, where its transcriptional activity and its expression level are regulated by post-traductional modifications. In first part of our project, we have shown the major mechanism leading to the nuclear degradation of MyoD. So, we have demonstrated that the ubiquitylation of MyoD is majoritarly realized on its Lysine 133, and seems to be also implicated in its myogenic activity. The second part of our study deals with MyoD regulation during G2/M transition. Thus, we have shown that MyoD is partially degraded in the end of the G2 phase independently of its D-box motif and of the ubiquitin ligase APCcdc20/cdh1. This degradation is only dependent of Serine 200 phosphorylation. Finally, we have also demonstrated that the double-phosphorylation of MyoD plays a major role in its transcriptional inhibition through a decreased ADN affinity leading to its chromatin exclusion in mitosis. Thus, MyoD appears to be tightly regulated during cell cycle by two highly specific mechanisms during G1/S and G2/M transitions. Therefore, our study participates to the understanding of MyoD regulation during the proliferation of Myoblasts, required for identifying in the future several pathological mechanisms involved in muscular diseases