title: Identification of a functional nuclear localization signal within the human USP22 protein.
abstract: Ubiquitin-specific processing enzyme 22 (USP22), a member of the deubiquitinase family, is over-expressed in most human cancers and has been implicated in tumorigenesis. Because it is an enzymatic subunit of the human SAGA transcriptional cofactor, USP22 deubiquitylates histone H2A and H2B in the nucleus, thus participating in gene regulation and cell-cycle progression. However, the mechanisms regulating its nuclear translocation have not yet been elucidated. It was here demonstrated that USP22 is imported into the nucleus through a mechanism mediated by nuclear localization signal (NLS). The bipartite NLS sequence KRELELLKHNPKRRKIT (aa152-168), was identified as the functional NLS for its nuclear localization. Furthermore, a short cluster of basic amino acid residues KRRK within this bipartite NLS plays the primary role in nuclear localization and is evolutionarily conserved in USP22 homologues. In the present study, a functional NLS and the minimal sequences required for the active targeting of USP22 to the nucleus were identified. These findings may provide a molecular basis for the mechanism underlying USP22 nuclear trafficking and function.
authors.affiliation: Key Laboratory of Jiangxi Province for the Systems Bio-Medicine, Jiujiang, Jiangxi Province 332000, China; College of Basic Medical Science, Jiujiang University, Jiujiang, Jiangxi Province 332000, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, Hubei Province 430060, China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Jiangxi Province for the Systems Bio-Medicine, Jiujiang, Jiangxi Province 332000, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gong
authors.affiliation: College of Basic Medical Science, Jiujiang University, Jiujiang, Jiangxi Province 332000, China.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Liu
authors.affiliation: College of Basic Medical Science, Jiujiang University, Jiujiang, Jiangxi Province 332000, China. Electronic address: lwd626518@163.com.
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000737:chemistry* / Q000502:physiology*; D017124:Conserved Sequence; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000737:chemistry* / Q000502:physiology*; D013329:Structure-Activity Relationship; D013869:Thiolester Hydrolases / Q000737:chemistry* / Q000502:physiology*; D043222:Ubiquitin Thiolesterase
chemical_list: D019913:Nuclear Localization Signals; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; C527170:Usp22 protein, human
keywords: HeLa; NLS; USP22