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TSPY and its X-encoded homologue interact with cyclin B but exert contrasting functions on cyclin-dependent kinase 1 activities

Oncogene volume 27, pages 6141–6150 (2008)Cite this article

A Corrigendum to this article was published on 23 April 2009

Abstract

Testis-specific protein Y-encoded (TSPY) is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY). TSPY and an X-homologue, TSPX, harbor a conserved domain, designated as SET/NAP domain, but differ at their C termini. Ectopic expression of TSPY accelerates cell proliferation by abbreviating the G2/M stage, whereas overexpression of TSPX retards cells at the same stage of the cell cycle. Previous studies demonstrated that the SET oncoprotein is capable of binding to cyclin B. Using various protein interaction techniques, we demonstrated that TSPY and TSPX indeed bind competitively to cyclin B at their SET/NAP domains in vitro and in vivo. TSPY colocalizes with cyclin B1 during the cell cycle, particularly on the mitotic spindles at metaphase. TSPY enhances while TSPX represses the cyclin B1–CDK1 phosphorylation activity. The inhibitory effect of TSPX on the cyclin B1–CDK1 complex has been mapped to its carboxyl acidic domain that is absent in TSPY, suggesting that TSPX could serve a normal function in modulating cell-cycle progression at the G2/M stage, whereas TSPY has acquired a specialized function in germ cell renewal and differentiation. Epigenetic dysregulation of TSPY in incompatible germ or somatic cells could promote cell proliferation and predispose susceptible cells to tumorigenesis.

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Acknowledgements

We thank Dr Tatsuo Kido for assistance in immunofluorescence of transfected cells presented in Figures 4f–h. This work was partially supported by a Merit Review grant and a Prostate Cancer REAP from the Department of Veterans Affairs and an Idea Grant from the Department of Defense to Y-FCL. Y-FC Lau is a research career scientist of the Department of Veterans Affairs.

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  1. Department of Medicine, VA Medical Center, University of California, San Francisco, San Francisco, CA, USA

    Y Li & Y-F Chris Lau

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Correspondence to Y-F Chris Lau.

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Li, Y., Lau, YF. TSPY and its X-encoded homologue interact with cyclin B but exert contrasting functions on cyclin-dependent kinase 1 activities. Oncogene 27, 6141–6150 (2008). https://doi.org/10.1038/onc.2008.206

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