Active maintenance of mHDA2/mHDAC6 histone-deacetylase in the cytoplasm.
The intracellular localization, and thereby the function, of a number of key regulator proteins tagged with a short leucine-rich motif (the nuclear export signal or NES) is controlled by CRM1/exportin1, which is involved in the export of these proteins from the nucleus [1]. A common characteristic of these regulators is their transient action in the nucleus during either a specific phase of the cell cycle or in response to specific signals [1]. Here, we show that a particular member of the class II histone-deacetylases mHDA2/mHDAC6 [2] belongs to this family of cellular regulators that are present predominantly in the cytoplasm, but are also capable of shuttling between the nucleus and the cytoplasm. A very potent NES present at the amino terminus of mHDAC6 was found to play an essential role in this shuttling process. The sub-cellular localization of mHDAC6 appeared to be controlled by specific signals, since the arrest of cell proliferation was found to be associated with the translocation of a fraction of the protein into the nucleus. Data presented here suggest that mHDAC6 might be the first member of a functionally distinct class of deacetylases, responsible for activities not shared by other known histone deacetylases.
Verdel
A
A
Laboratoire de Biologie Moléculaire et Cellulaire de la Différenciation, INSERM U309, La Tronche, France.
Curtet
S
S
Brocard
M P
MP
Rousseaux
S
S
Lemercier
C
C
Yoshida
M
M
Khochbin
S
S
D000595:Amino Acid Sequence; D003593:Cytoplasm / Q000201:enzymology*; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data
D006655:Histone Deacetylases