Phosphorylation Of Ap-2α By The Ck2 Kinase Results In Repression Of Ap-2α-mediated Transcriptional Activity

The AP-2 transcription factor family consisting of five related factors, AP-2α,AP-2β,AP-2γ,AP-2δand AP-2ε,orchestrates a variety of cell processes including apoptosis, cell growth, and tissue differentiation during embryogenesis. The proteins have a characteristic helix-span-helix motif at the carboxyl terminus, which together with a central basic region, mediates dimerization and DNA binding. The amino terminus contains the transactivation domain. Previous research demonstrated that the exprssion level of AP-2 is highly associated with tumorigenesis. For example, the overexpression of AP-2 is observed in breast cancer and ovary carcinomas while the loss of expression of AP-2 is detected in melanoma and gliomas. Both interaction with various proteins and post-translational phosphorylation play an important role in controlling the activity of AP-2 proteins. We have identified a direct protein-protein interaction between AP-2a and CK2β. The interaction between AP-2αand CK2βwas demonstrated in vitro by GST pull-down and was confirmed in vivo by co-immunoprecipitation. Analysis of phosphorylation revealed that AP-2αwas phosphorylated by CK2 kinase in vitro and the phosphorylation site of AP-2a protein was Ser429. Further studies indicated that the phosphorylation of AP-2a by CK2 kinase resulted in the repression of AP-2α-mediated transcriptional activity and the degradation of AP-2a protein probably accounted for the repression. Our observation provides a mechanism for temporal and spatial regulation of AP-2αexpression and functions and adds weight to understand pivotal regulatory role of AP-2αin a variety of significant cell processes.