Protein kinase C-related kinase targets nuclear localization signals in a subset of class IIa histone deacetylases.
Class IIa histone deacetylases (HDACs) -4, -5, -7 and -9 undergo signal-dependent nuclear export upon phosphorylation of conserved serine residues that are targets for 14-3-3 binding. Little is known of other mechanisms for regulating the subcellular distribution of class IIa HDACs. Using a biochemical purification strategy, we identified protein kinase ... C-related kinase-2 (PRK2) as an HDAC5-interacting protein. PRK2 and the related kinase, PRK1, phosphorylate HDAC5 at a threonine residue (Thr-292) positioned within the nuclear localization signal (NLS) of the protein. HDAC7 and HDAC9 contain analogous sites that are phosphorylated by PRK, while HDAC4 harbors a non-phosphorylatable alanine residue at this position. We provide evidence to suggest that the unique phospho-acceptor cooperates with the 14-3-3 target sites to impair HDAC nuclear import.
Mesh Terms:
14-3-3 Proteins, Active Transport, Cell Nucleus, Amino Acid Sequence, Animals, COS Cells, Catalytic Domain, Cells, Cultured, Cercopithecus aethiops, Consensus Sequence, Histone Deacetylases, Humans, Models, Biological, Nuclear Localization Signals, Phosphorylation, Protein Binding, Protein Interaction Mapping, Protein Kinase C
14-3-3 Proteins, Active Transport, Cell Nucleus, Amino Acid Sequence, Animals, COS Cells, Catalytic Domain, Cells, Cultured, Cercopithecus aethiops, Consensus Sequence, Histone Deacetylases, Humans, Models, Biological, Nuclear Localization Signals, Phosphorylation, Protein Binding, Protein Interaction Mapping, Protein Kinase C
FEBS Lett.
Date: Mar. 19, 2010
PubMed ID: 20188095
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