title: Protein kinase CK2 regulates the dimerization of histone deacetylase 1 (HDAC1) and HDAC2 during mitosis.
abstract: Histone deacetylase 1 (HDAC1) and HDAC2 are components of corepressor complexes that are involved in chromatin remodeling and regulation of gene expression by regulating dynamic protein acetylation. HDAC1 and -2 form homo- and heterodimers, and their activity is dependent upon dimer formation. Phosphorylation of HDAC1 and/or HDAC2 in interphase cells is required for the formation of HDAC corepressor complexes. In this study, we show that during mitosis, HDAC2 and, to a lesser extent, HDAC1 phosphorylation levels dramatically increase. When HDAC1 and -2 are displaced from the chromosome during metaphase, they dissociate from each other, but each enzyme remains in association with components of the HDAC corepressor complexes Sin3, NuRD, and CoREST as homodimers. Enzyme inhibition studies and mutational analyses demonstrated that protein kinase CK2-catalyzed phosphorylation of HDAC1 and -2 is crucial for the dissociation of these two enzymes. These results suggest that corepressor complexes, including HDAC1 or HDAC2 homodimers, might target different cellular proteins during mitosis.
authors.affiliation: Manitoba Institute of Child Health, University of Manitoba, Winnipeg, Manitoba R3E 3P4, Canada.
authors.forename: Dilshad H
authors.initials: DH
authors.lastname: Khan
authors.affiliation: Manitoba Institute of Child Health, University of Manitoba, Winnipeg, Manitoba R3E 3P4, Canada.
authors.forename: Shihua
authors.initials: S
authors.lastname: He
authors.affiliation: Melanoma Medical Oncology, M.D. Anderson Cancer Center, Houston, Texas 77054.
authors.forename: Jenny
authors.initials: J
authors.lastname: Yu
authors.affiliation: Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, 1030 Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Winter
authors.affiliation: Manitoba Institute of Child Health, University of Manitoba, Winnipeg, Manitoba R3E 3P4, Canada.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Cao
authors.affiliation: Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, 1030 Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Seiser
authors.affiliation: Manitoba Institute of Child Health, University of Manitoba, Winnipeg, Manitoba R3E 3P4, Canada. Electronic address: davie@cc.umanitoba.ca.
authors.forename: James R
authors.initials: JR
authors.lastname: Davie
mesh_terms: D047389:Casein Kinase I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002877:Chromosomes, Human / Q000201:enzymology* / Q000235:genetics; D056970:Co-Repressor Proteins; D057809:HEK293 Cells; D006367:HeLa Cells; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism*; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D055503:Protein Multimerization / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D056264:Sin3 Histone Deacetylase and Corepressor Complex / Q000235:genetics / Q000378:metabolism
chemical_list: D056970:Co-Repressor Proteins; D009419:Nerve Tissue Proteins; C121019:RCOR1 protein, human; D012097:Repressor Proteins; D047389:Casein Kinase I; C110550:HDAC1 protein, human; C533423:HDAC2 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D056264:Sin3 Histone Deacetylase and Corepressor Complex
keywords: Corepressor Transcription; HDAC2 Phosphorylation; Histone Deacetylase; Mitosis; Protein Kinase CK2; Protein Kinases; Protein Phosphorylation