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 biochemi...

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Bibliographic Details
Published in:FEBS letters 2010-03, Vol.584 (6), p.1103-1110
Main Authors: Harrison, Brooke C., Huynh, Khai, Lundgaard, Greta L., Helmke, Steven M., Perryman, M. Benjamin, McKinsey, Timothy A.
Format: Article
Language:English
Subjects:
14-3-3 Proteins - metabolism
Active Transport, Cell Nucleus - physiology
Amino Acid Sequence
Animals
Catalytic Domain
Cells, Cultured
Cercopithecus aethiops
Consensus Sequence
COS Cells
Histone deacetylase
Histone Deacetylases - chemistry
Histone Deacetylases - metabolism
Humans
Kinase
Models, Biological
Nuclear localization
Nuclear Localization Signals - metabolism
Phosphorylation
Protein Binding
Protein Interaction Mapping
Protein Kinase C - metabolism
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Summary: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. MINT-7710106:HDAC5 (uniprotkb:Q9UQL6) physically interacts (MI:0915) with PRK2 (uniprotkb:Q16513) by pull down (MI:0096)
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2010.02.057