Mammalian histone deacetylase 1 protein is posttranslationally modified by phosphorylation.

HDAC1, a member of the histone deacetylase family, is involved in transcription regulation through the modification of chromatin structure. Several studies also implicated HDAC1 in tumorigenesis. Much attention has been concentrated on protein-protein interactions involving HDAC1 and the possibility that posttranslational modifications may occur in mammalian HDAC1 proteins has not been carefully and systematically investigated. In this study, we utilized in vivo labeling assays to demonstrate that both human and murine HDAC1 proteins are phosphorylated in cells. Assays using HDAC1 deletion mutants indicated that phosphorylation occurs in its C-terminal domain. cAMP-dependent kinase and casein kinase II, but not protein kinase C, cdc2, or MAP kinase, could phosphorylate HDAC1 in vitro, although HDAC1 contains several protein kinase C consensus sites. We also found that phosphorylation did not influence HDAC1 enzymatic activity using a human histone H4 N-terminal peptide as the substrate. Interestingly, HDAC1-FLAG fusion protein immunoprecipitated from transfected cells was found to be in association with a kinase activity, providing an in vitro assay for further studies of this posttranslational modification.