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Protein kinase C-related kinase targets nuclear localization signals in a subset of class IIa histone deacetylases |
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| Authors: | Brooke C. Harrison Greta L. Lundgaard M. Benjamin Perryman |
| Affiliation: | a Gilead Colorado, Inc., Boulder, CO, USA b Department of Pediatrics, University of Colorado at Denver, Aurora, CO, USA c Cardiovascular Research Center, Sanford Research/USD, Sioux Falls, South Dakota, USA d Division of Cardiology, University of Colorado, Denver, Aurora, CO, USA |
| Abstract: | 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.Structured summaryMINT-7710106:HDAC5 (uniprotkb:Q9UQL6) physically interacts (MI:0915) with PRK2 (uniprotkb:Q16513) by pull down (MI:0096) |
| Keywords: | Kinase Phosphorylation Histone deacetylase Nuclear localization |
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