Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Histone deacetylase 3 (HDAC3) activity is regulated by interaction with protein serine/threonine phosphatase 4.

Genes & development | Apr 1, 2005

Histone deacetylase 3 (HDAC3) is one of four members of the human class I HDACs that regulates gene expression by deacetylation of histones and nonhistone proteins. Early studies have suggested that HDAC3 activity is regulated by association with the corepressors N-CoR and SMRT. Here we demonstrate that, in addition to protein-protein interactions with NCoR/SMRT, the activity of HDAC3 is regulated by both phosphorylation and dephosphorylation. A protein kinase CK2 phosphoacceptor site in the HDAC3 protein was identified at position Ser424, which is a nonconserved residue among the class I HDACs. Mutation of this residue was found to reduce deacetylase activity. Interestingly, unlike other class I HDACs, HDAC3 uniquely copurifies with the catalytic and regulatory subunits of the protein serine/threonine phosphatase 4 complex (PP4c/PP4R1). Furthermore, HDAC3 complexes displayed protein phosphatase activity and a series of subsequent mutational analyses revealed that the N terminus of HDAC3 (residues 1-122) was both necessary and sufficient for HDAC3-PP4c interactions. Significantly, both overexpression and siRNA knock-down approaches, and analysis of cells devoid of PP4c, unequivocally show that HDAC3 activity is inversely proportional to the cellular abundance of PP4(c). These findings therefore further highlight the importance of protein-protein interactions and extend the significance of dephosphorylation in the regulation of HDAC activity, as well as present a novel alternative pathway by which HDAC3 activity is regulated.

Pubmed ID: 15805470 RIS Download

Mesh terms: Amino Acid Sequence | Casein Kinase II | Histone Deacetylases | Humans | Molecular Sequence Data | Phosphoprotein Phosphatases | Phosphorylation | Protein Structure, Tertiary | Serine

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: R01 CA109699
  • Agency: NIGMS NIH HHS, Id: R01 GM058486
  • Agency: NCI NIH HHS, Id: CA109699
  • Agency: NIGMS NIH HHS, Id: GM58486

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.