14-3-3 regulates the nuclear import of class IIa histone deacetylases
- Chemical Genetics Laboratory/Chemical Genomics Research Group, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)
- Department of Biotechnology, University of Tokyo, Bunkyo-ku, Tokyo 113-8657 (Japan)
- Department of Molecular Pharmacology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, 305-8575 (Japan)
Class IIa histone deacetylases (HDACs) form complexes with a class of transcriptional repressors in the nucleus. While screening for compounds that could block the association of HDAC4 with the BTB domain-containing transcriptional repressor Bach2, we discovered that phorbol 12-myristate 13-acetate (PMA) induced the cytoplasmic retention of HDAC4 mutants lacking a nuclear export signal (NES). Although PMA treatment and PKD overexpression has been proposed to facilitate the nuclear export of class IIa HDACs by creating 14-3-3 binding sites containing phosphoserines, our experiments using HDAC mutants demonstrated that PMA greatly reduces nuclear import. PMA treatment repressed the NLS activity in a manner dependent on 14-3-3 binding. These results suggest that nuclear HDAC4 is not tethered in the nucleus, but instead shuttles between the nucleus and the cytoplasm. Phosphorylation-induced 14-3-3 binding biases the balance of nucleo-cytoplasmic shuttling toward the cytoplasm by inhibiting nuclear import.
- OSTI ID:
- 21255795
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 377, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2008.10.079; PII: S0006-291X(08)02033-0; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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