title: Interphase nucleo-cytoplasmic shuttling and localization of SIRT2 during mitosis.
abstract: The human NAD+-dependent protein deacetylase SIRT2 resides predominantly in the cytoplasm where it functions as a tubulin deacetylase. Here we report that SIRT2 maintains a largely cytoplasmic localization during interphase by active nuclear export in a Crm1-dependent manner. We identified a functional, leptomycin B-sensitive, nuclear export signal sequence within SIRT2. During the cell cycle, SIRT2 becomes enriched in the nucleus and is associated with mitotic structures, beginning with the centrosome during prophase, the mitotic spindle during metaphase, and the midbody during cytokinesis. Cells overexpressing wild-type or a catalytically inactive SIRT2 exhibit an increase in multinucleated cells. The findings suggest a novel mechanism of regulating SIRT2 function by nucleo-cytoplasmic shuttling, as well as a role for SIRT2 in the nucleus during interphase and throughout mitosis.
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California at San Francisco, California, United States of America.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: North
authors.forename: Eric
authors.initials: E
authors.lastname: Verdin
mesh_terms: D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007399:Interphase / Q000502:physiology*; D008938:Mitosis; D049790:Nuclear Export Signals; D056565:Sirtuin 2 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D005231:Fatty Acids, Unsaturated; D049790:Nuclear Export Signals; C474199:SIRT2 protein, human; D056565:Sirtuin 2; C038753:leptomycin B