title: Phosphorylation of the histone deacetylase 7 modulates its stability and association with 14-3-3 proteins.
abstract: Class II histone deacetylases (HDACs) play a role in myogenesis and inhibit transcriptional activation by myocyte enhancer factors 2. A distinct feature of class II HDACs is their ability to shuttle between the nucleus and the cytoplasm in a cell type- and signal-dependent manner. We demonstrate here that treatment with the 26 S proteosome inhibitors, MG132 and ALLN, leads to detection of ubiquitinated HDAC7 and causes accumulation of cytoplasmic HDAC7. We also show that treatment with calyculin A, a protein phosphatase inhibitor, leads to a marked increase of HDAC7 but not HDAC5. The increase in HDAC7 is accompanied by enhanced interaction between 14-3-3 proteins and HDAC7. HDAC7 mutations that prevent the interaction with 14-3-3 proteins also block calyculin A-mediated stabilization. Expression of constitutively active calcium/calmodulin-dependent kinase I stabilizes HDAC7 and causes an increased association between HDAC7 and 14-3-3. Together, our results suggest that calcium/calmodulin-dependent kinase I-mediated phosphorylation of HDAC7 acts, in part, to promote association of HDAC7 with 14-3-3 and stabilizes HDAC7.
authors.affiliation: Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Li
authors.forename: Song
authors.initials: S
authors.lastname: Song
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Ko
authors.forename: Hung-Ying
authors.initials: HY
authors.lastname: Kao
mesh_terms: D048948:14-3-3 Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008387:Marine Toxins; D008954:Models, Biological; D009154:Mutation; D010080:Oxazoles / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D014176:Protein Biosynthesis; D013997:Time Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D048948:14-3-3 Proteins; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D007976:Leupeptins; D008387:Marine Toxins; D010080:Oxazoles; C063261:acetylleucyl-leucyl-norleucinal; C059041:calyculin A; D014446:Tyrosine 3-Monooxygenase; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C543273:HDAC7 protein, human; D006655:Histone Deacetylases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde