Phosphorylation of the histone deacetylase 7 modulates its stability and association with 14-3-3 proteins.

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.
Mesh Terms:
14-3-3 Proteins, Cell Line, Cell Nucleus, Cysteine Proteinase Inhibitors, Cytoplasm, Enzyme Inhibitors, Histone Deacetylases, Humans, Leupeptins, Models, Biological, Mutation, Oxazoles, Peptide Hydrolases, Phosphorylation, Plasmids, Proteasome Endopeptidase Complex, Protein Binding, Protein Biosynthesis, Time Factors, Transcription, Genetic, Transcriptional Activation, Transfection, Tyrosine 3-Monooxygenase, Up-Regulation
J. Biol. Chem.
Date: Aug. 13, 2004
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