title: Protein kinase CK2 regulates the formation and clearance of aggresomes in response to stress.
abstract: Misfolded protein aggregates elicit a stress response, and their clearance is crucial for cell survival. These aggregates are transported by cytoplasmic deacetylase HDAC6 and dynein motors to the aggresome via the microtubule network, and are removed by autophagic degradation. HDAC6 activity is necessary for both the transport and clearance of protein aggregates. However, the cellular factors that regulate HDAC6 activity remain unknown. Here we show that protein kinase CK2 is a crucial modulator of HDAC6 activity because CK2 directly phosphorylates HDAC6 and increases cytoplasmic deacetylase activity. Indeed, cells that expressed HDAC6 mutated at Ser458, a CK2-mediated phosphorylation site, failed to both form and clear aggresomes, and increased cytotoxicity. Interestingly, Ser458 is conserved only in higher primates, such as human and chimpanzee, but not in the rhesus macaque. These findings identify CK2 as a crucial protein involved in the formation and clearance of aggresomes, and hence in cell viability in response to misfolded protein stress.
authors.affiliation: Department of Pharmacology, Teikyo University School of Medicine, Tokyo 173-8605, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watabe
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakaki
mesh_terms: D000818:Animals; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D053938:DNA Fragmentation; D004591:Electrophoresis, Polyacrylamide Gel; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D002679:Pan troglodytes; D019606:Phosphoamino Acids / Q000378:metabolism; D010766:Phosphorylation / Q000235:genetics / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics / Q000502:physiology
chemical_list: D019606:Phosphoamino Acids; D034741:RNA, Small Interfering; D047390:Casein Kinase II; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases