Protein kinase DYRK2 is a scaffold that facilitates assembly of an E3 ligase

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Abstract
The kinase DYRK2 regulates the assembly of a ubiquitin ligase complex in a phosphorylation-independent manner, while also phosphorylating the target for the ligase. Thus, ligase assembly and target ubiquitylation appear to be physically linked processes. Protein kinases have central functions in various cellular signal transduction pathways through their substrate phosphorylation. Here we show that a protein kinase, DYRK2, has unexpected role as a scaffold 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 scaffold for the EDVP complex, because small-interfering-RNA-mediated depletion of DYRK2 disrupts the formation of the EDD–DDB1–VPRBP complex. 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 in humans that depends on a protein kinase for complex formation as well as for the subsequent phosphorylation, ubiquitylation and degradation of their substrates.