Regulation of histone deacetylase 2 by protein kinase CK2.
Histone deacetylase 2 (HDAC2) is a member of a large family of enzymes that alter gene expression by catalyzing the removal of acetyl groups from core histones. Originally isolated as a transcriptional co-repressor, HDAC2 possesses extensive amino acid sequence homology to HDAC1 (the founding member and most extensively studied HDAC enzyme). Because of this high degree of sequence similarity between HDAC1 and HDAC2, coupled with the fact that the two always co-exist in the same complexes, it is difficult to assess whether different properties exist between these two proteins. We report here that HDAC2 is a phosphoprotein similar to HDAC1. In addition, like HDAC1, the phospho-acceptor sites in HDAC2 are located in the C-terminal portion of the protein. However, unlike HDAC1, which can be phosphorylated by protein kinase CK2, cAMP-dependent protein kinase, and protein kinase G, HDAC2 is phosphorylated uniquely by protein kinase CK2 in vitro. Studies using unfractionated cell extracts with CK2 inhibitors suggest that protein kinase CK2 is the major source of HDAC2 kinase. Finally, and perhaps most interesting, HDAC2 phosphorylation promotes enzymatic activity, selectively regulates complex formation, but has no effect on transcriptional repression. Together, our data indicate that like many HDACs, HDAC2 is regulated by post-translational modification, particularly phosphorylation. Furthermore, we demonstrate for the first time that there are similarities and differences in the regulation of HDAC1 and HDAC2 by phosphorylation.
Tsai
Shih-Chang
SC
H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida 33612, USA.
Seto
Edward
E
D000595:Amino Acid Sequence; D047310:Apigenin; D047390:Casein Kinase II; D004794:Enzyme Repression; D005419:Flavonoids / Q000494:pharmacology; D006367:HeLa Cells; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000737:chemistry; D010750:Phosphoproteins / Q000378:metabolism; D010768:Phosphoserine / Q000032:analysis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012097:Repressor Proteins; D014158:Transcription, Genetic
D005419:Flavonoids; D010748:Phosphopeptides; D010750:Phosphoproteins; D012097:Repressor Proteins; D010768:Phosphoserine; D047310:Apigenin; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases