Protein kinase DYRK2 is a scaffold that facilitates assembly of an E3 ligase.
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.
Maddika
Subbareddy
S
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Chen
Junjie
J
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D006367:HeLa Cells; D006801:Humans; D000074201:Katanin; D008938:Mitosis; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013379:Substrate Specificity; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D000097603:Dyrk Kinases
D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases; D000074201:Katanin; D046912:Multiprotein Complexes; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D044767:Ubiquitin-Protein Ligases; D000097603:Dyrk Kinases