title: Subnuclear distribution of SSX regulates its function.
abstract: SSX, a family of genes clustered on the X chromosome, has been identified as a cancer-testis antigen and also forms a part of the SYT-SSX fusion gene found in synovial sarcoma, implying that it has an important role in tumorigenesis. However, knowledge of the molecular regulation of SSX is still limited. In this study, we demonstrate that SSX or its SYT fusion protein is distributed as nuclear speckles, in which it is co-localized with B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1), which is a core factor of polycomb repressor complex 1. The C-terminal residues of SSX are indispensable for the nuclear speckle distribution, while the N-terminal domain is necessary for the recruitment of Bmi1, indicating that intact SSX must be needed for interaction with Bmi1 both spatially and functionally. In addition, the N-terminus of SSX also proved to contain an intrinsic nucleolar localization signal, which mediates the nucleolar translocation of SSX in particular kinds of cell stress such as the oxidation of hydrogen peroxide or heat shock. This stress-induced translocation is reversible and accompanied by HSP 70 or p14ARF traffic, suggesting that SSX is a stress response gene. It is of note that nucleolar translocation of SSX can result in disassociation of SSX from Bmi1, with consequent down-regulation of Bmi1 activity. These novel findings regarding distinct domains of SSX and its interaction with Bmi1 may shed light on the mechanism by which synovial sarcoma develops and on the up-regulation of SSX in cancer cells.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Health Science Center of Peking University, Haidian District, Beijing, China.
authors.forename: Jiaochen
authors.initials: J
authors.lastname: Wang
authors.forename: Huali
authors.initials: H
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Hou
authors.forename: Haijing
authors.initials: H
authors.lastname: Liu
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Zou
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.forename: Michael A
authors.initials: MA
authors.lastname: McNutt
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
mesh_terms: D002451:Cell Compartmentation / Q000187:drug effects; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D013312:Stress, Physiological / Q000187:drug effects; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism
chemical_list: C069077:BMI1 protein, human; D018840:HSP70 Heat-Shock Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D025803:Tumor Suppressor Protein p14ARF; D049452:Green Fluorescent Proteins; C093962:synovial sarcoma X breakpoint proteins; D006861:Hydrogen Peroxide; D063150:Polycomb Repressive Complex 1