TI - Phosphorylation of nuclear MyoD is required for its rapid degradation . AB - MyoD is a basic helix-loop-helix transcription factor involved in the activation of genes encoding skeletal muscle-specific proteins . Independent of its ability to transactivate muscle-specific genes , MyoD can also act as a cell cycle inhibitor . MyoD activity is regulated by transcriptional and posttranscriptional mechanisms . While MyoD can be found phosphorylated , the functional significance of this posttranslation modification has not been established . MyoD contains several consensus cyclin-dependent kinase ( CDK ) phosphorylation sites . In these studies , we examined whether a link could be established between MyoD activity and phosphorylation at putative CDK sites . Site -directed mutagenesis of potential CDK phosphorylation sites in MyoD revealed that S200 is required for MyoD hyperphosphorylation as well as the normally short half-life of the MyoD protein . Additionally , we determined that turnover of the MyoD protein requires the proteasome and Cdc34 ubiquitin-conjugating enzyme activity . Results of these studies demonstrate that hyperphosphorylated MyoD is targeted for rapid degradation by the ubiquitin pathway . The targeted degradation of MyoD following CDK phosphorylation identifies a mechanism through which MyoD activity can be regulated coordinately with the cell cycle machinery ( CDK2 and CDK4 ) and/or coordinately with the cellular transcriptional machinery ( CDK7 , CDK8 , and CDK9 ) .