Study On SUMOylation Of CDK9

SUMOylation, a common post-translational modification of proteins, has important biological functions and is related to cancer and other diseases. A wide-range of proteins can be SUMO modified, including transcription factors and co-transcription factors (coactivator and corepresssor). SUMO modification influences the transcription activities of various transcription factors. In general, SUMO modification leads to transcriptional repression. While the transcriptional repression by SUMOylation has been linked to enhanced HDAC activity, we have observed an HDAC-independent mechanism for SUMO-mediated transcriptional repression.We discovered that CDK9 kinase can be sumoylated both in vitro and in cells. SUMOylation of CDK9 reduces its kinase activity, thereby resulting in a decreased level of phosphorylated Ser2 in the CTD domain of RNA pol Ⅱ and consequently reduced transcription. Moreover, this decreased transcriptional level is not gene specific. During the process, phosphorylation of Ser5 in the CTD domain is not affected. Further studies show that transcription factor c-Myc can inhibit the SUMOylation of CDK9 in a dose-dependent manner, which leads to the increasing in CDK9 kinase activity. Our data provide new evidence for a role of c-Myc in the general amplification of transcriptional activity in cells..Overall, we find that CDK9 kinase is a novel SUMOylated protein and that CDK9 SUMOylation has a universal role in transcriptional repression. Our study therefore reveals a novel mechanism for SUMO-mediated transcriptional repression.