Protein kinase DYRK2 is an E3-ligase specific molecular assembler

Protein kinases play central roles in diverse cellular signal transduction pathways via their substrate phosphorylation. In this study, we discover that a protein kinase DYRK2 has unexpected role as a molecular assembler for an E3-ubiquitin ligase complex. DYRK2 associates with an E3 ligase complex containing EDD, DDB1 and VPRBP proteins (EDVP complex). Strikingly, DYRK2 serves as a molecular assembler for the EDVP complex as siRNA mediated depletion of DYRK2 disrupts the EDD-DDB1/VPRBP complex formation. Although the kinase activity of DYRK2 is dispensable for its ability to mediate EDVP complex formation, it is required for the phosphorylation and subsequent degradation of its downstream substrate, Katanin p60. Collectively, our results reveal a new type of E3-ubiquitin ligase complex that depends on a protein kinase for complex formation as well as for the subsequent phosphorylation, ubiquitination and degradation of their substrates.