calyculin-a and acetylleucyl-leucyl-norleucinal

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.

Topics: 14-3-3 Proteins; Cell Line; Cell Nucleus; Cysteine Proteinase Inhibitors; Cytoplasm; Enzyme Inhibitors; Histone Deacetylases; Humans; Leupeptins; Marine Toxins; 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