title: Cytoplasm-localized SIRT1 enhances apoptosis.
abstract: In general, SIRT1 is localized in nuclei. Here, we showed that endogenous and exogenous SIRT1 were both able to partially localize in cytoplasm in certain cell lines, and cytoplasm-localized SIRT1 was associated with apoptosis and led to increased sensitivity to apoptosis. Furthermore, we demonstrated that translocation of nucleus-localized SIRT1 from nuclei to cytoplasm was the main pathway leading to localization of SIRT1 in cytoplasm. In HeLa cells, wild type SIRT1 was completely localized in nuclei. By truncation of two predicted nuclear localization signals or fusion with an exogenous nuclear export signal, SIRT1 was partially localized in cytoplasm of HeLa cells and resulted in increased sensitivity to apoptosis. The apoptosis enhanced by cytoplasm-localized SIRT1 was independent of its deacetylase activity, but dependent on caspases. SIRT1 was distributed in cytoplasm at metaphase during mitosis, and overexpression of SIRT1 significantly augmented apoptosis for cells at metaphase. In summary, we found SIRT1 is able to localize in cytoplasm, and cytoplasm-localized SIRT1 enhances apoptosis.
authors.affiliation: Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Qihuang
authors.initials: Q
authors.lastname: Jin
authors.forename: Tingting
authors.initials: T
authors.lastname: Yan
authors.forename: Xinjian
authors.initials: X
authors.lastname: Ge
authors.forename: Cheng
authors.initials: C
authors.lastname: Sun
authors.forename: Xianglin
authors.initials: X
authors.lastname: Shi
authors.forename: Qiwei
authors.initials: Q
authors.lastname: Zhai
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase; D049790:Nuclear Export Signals / Q000235:genetics; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D017931:DNA Primers; D049790:Nuclear Export Signals; D019913:Nuclear Localization Signals; D011993:Recombinant Fusion Proteins; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins