title: Protein kinase CK2-mediated phosphorylation of HDAC2 regulates co-repressor formation, deacetylase activity and acetylation of HDAC2 by cigarette smoke and aldehydes.
abstract: Histone deacetylase 2 (HDAC2) mediates the repression of pro-inflammatory genes by deacetylating core histones, RelA/p65 and the glucocorticoid receptor. Reduced level of HDAC2 is associated with steroid resistant inflammation caused by cigarette smoke (CS)-derived oxidants and aldehydes. However, the molecular mechanisms regulating HDAC2 in response to CS and aldehydes is not known. Here, we report that CS extract, and aldehyde acrolein induced phosphorylation of HDAC2 which was abolished by mutations at serine sites S(394), S(411), S(422) and S(424). HDAC2 phosphorylation required direct interaction with serine-phosphorylated protein kinase CK2alpha and involved reduced HDAC2 deacetylase activity. Furthermore, HDAC2 phosphorylation was required for HDAC2 interaction with transcription factors, co-repressor complex formation, CBP recruitment, acetylation on lysine residues and modulates transrepression activity. Thus, phospho-acetylation of HDAC2 negatively regulates its deacetylase activity which has implications in steroid resistance in chronic inflammatory conditions.
authors.affiliation: Department of Environmental Medicine, University of Rochester Medical Center, NY 14642, USA.
authors.forename: David
authors.initials: D
authors.lastname: Adenuga
authors.forename: Irfan
authors.initials: I
authors.lastname: Rahman
mesh_terms: D000107:Acetylation; D000447:Aldehydes / Q000494:pharmacology*; D050882:CREB-Binding Protein / Q000378:metabolism; D047390:Casein Kinase II / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D002460:Cell Line; D045424:Complex Mixtures / Q000494:pharmacology; D020868:Gene Silencing; D056464:Histone Deacetylase 2 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport; D012097:Repressor Proteins / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D012906:Smoke; D014026:Nicotiana
chemical_list: D000447:Aldehydes; D045424:Complex Mixtures; D012097:Repressor Proteins; D012906:Smoke; D012694:Serine; D050882:CREB-Binding Protein; D047390:Casein Kinase II; D010744:Phosphoric Monoester Hydrolases; D056464:Histone Deacetylase 2
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