CRM1 mediates nuclear export of HDAC7 independently of HDAC7 phosphorylation and association with 14-3-3s.
CRM1, 14-3-3 proteins, and CaMK play important roles in trafficking of HDAC7, but the interplay between these proteins in this process is not clearly understood. Here, we show that CRM1 is capable of promoting cytoplasmic localization of wild-type and mutant HDAC7 (S178A/S344A/S479A), which is normally found in the nucleus. Using phospho-specific antibodies to HDAC7, we demonstrate that CaMK I promotes phosphorylation of S178, S344, and S479 of HDAC7. We also show that endogenous S178-phosphorylated HDAC7 is localized in both the nucleus and the cytoplasm, whereas S344- and S479-phosphorylated HDAC7 are exclusively localized in the nucleus. An HDAC7 mutant, S178E/S344E/S479E, which lost the ability to bind 14-3-3s, is localized in both the nucleus and the cytoplasm. Furthermore, the nuclear export of S178E/S344E/S479E is inhibited by LMB, but is enhanced by the CRM1. Taken together, these results strongly suggest that CRM1 mediated-nuclear export of HDAC7 is independent of HDAC7 phosphorylation and its association with 14-3-3s.
Gao
Chengzhuo
C
Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Li
Xiaofang
X
Lam
Minh
M
Liu
Yu
Y
Chakraborty
Sharmistha
S
Kao
Hung-Ying
HY
D048948:14-3-3 Proteins / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus; D000818:Animals; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000378:metabolism*; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000097606:Exportin 1 Protein
D048948:14-3-3 Proteins; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D006655:Histone Deacetylases; D028884:Karyopherins; D050505:Mutant Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein; C517596:CAMK1 protein, human; C517598:Camk1 protein, mouse; C517681:Pnck protein, mouse; C543273:HDAC7 protein, human; C543274:Hdac7 protein, mouse