FEBS Letters
Volume 584, Issue 6 , Pages 1103-1110, 19 March 2010

Protein kinase C-related kinase targets nuclear localization signals in a subset of class IIa histone deacetylases

Edited by Ivan Sadowski

  • Brooke C. Harrison

      Affiliations

    • Gilead Colorado, Inc., Boulder, CO, USA
    • ,
  • Khai Huynh

      Affiliations

    • Gilead Colorado, Inc., Boulder, CO, USA
    • ,
  • Greta L. Lundgaard

      Affiliations

    • Gilead Colorado, Inc., Boulder, CO, USA
    • ,
  • Steven M. Helmke

      Affiliations

    • Department of Pediatrics, University of Colorado at Denver, Aurora, CO, USA
    • ,
  • M. Benjamin Perryman

      Affiliations

    • Cardiovascular Research Center, Sanford Research/USD, Sioux Falls, South Dakota, USA
    • ,
  • Timothy A. McKinsey

      Affiliations

    • Gilead Colorado, Inc., Boulder, CO, USA
    • Division of Cardiology, University of Colorado, Denver, Aurora, CO, USA
    • Corresponding Author InformationCorresponding author. Address: Division of Cardiology, University of Colorado Health Sciences Center, 12700 E 19th Avenue, Rm 8014 A, Aurora, CO, USA.

Received 15 December 2009; received in revised form 5 February 2010; accepted 17 February 2010. published online 24 February 2010.

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 summary

MINT-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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PII: S0014-5793(10)00161-4

doi:10.1016/j.febslet.2010.02.057

FEBS Letters
Volume 584, Issue 6 , Pages 1103-1110, 19 March 2010

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