TSPY and its X-encoded homologue interact with cyclin B but exert contrasting functions on cyclin-dependent kinase 1 activities.
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 G(2)/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 G(2)/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.
Li
Y
Y
Department of Medicine, VA Medical Center, University of California, San Francisco, San Francisco, CA 94121, USA.
Lau
Y-F Chris
YF
D001665:Binding Sites; D001667:Binding, Competitive; D016203:CDC2 Protein Kinase / Q000032:analysis / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000502:physiology*; D019926:Cyclin B / Q000032:analysis / Q000502:physiology*; D004268:DNA-Binding Proteins; D044127:Epigenesis, Genetic; D016195:G2 Phase; D056488:Histone Chaperones; D006801:Humans; D009369:Neoplasms / Q000209:etiology; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D008941:Spindle Apparatus / Q000737:chemistry; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D019926:Cyclin B; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; C513473:SET protein, human; C497749:TSPY1 protein, human; D014157:Transcription Factors; D016203:CDC2 Protein Kinase