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Molecular and Cellular Biochemistry

, Volume 381, Issue 1–2, pp 17–29 | Cite as

Subnuclear distribution of SSX regulates its function

  • Jiaochen Wang
  • Huali Wang
  • Wei Hou
  • Haijing Liu
  • Yongxin Zou
  • Hong Zhang
  • Lin Hou
  • Michael A. McNutt
  • Bo Zhang
Article

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.

Keywords

SSX Bmi1 Nuclear speckle Nucleolus Protein traffic Cell stress 

Notes

Acknowledgments

This project (No. 3077830, No. 30570691, No. 81171907) supported by National Natural Science Foundation of China, and the Research Fund for the Doctoral Program of Higher Education (200800010060).

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Jiaochen Wang
    • 1
  • Huali Wang
    • 1
  • Wei Hou
    • 1
  • Haijing Liu
    • 1
  • Yongxin Zou
    • 1
  • Hong Zhang
    • 1
  • Lin Hou
    • 1
  • Michael A. McNutt
    • 1
  • Bo Zhang
    • 1
  1. 1.Department of Pathology, School of Basic Medical SciencesHealth Science Center of Peking UniversityBeijingChina

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