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.

Rasmussen's syndrome is a progressive and intractable form of epilepsy characterized pathologically by focal brain inflammation with large numbers of infiltrating T lymphocytes. To better understand the nature of the T cell response in this disease, we analyzed TCR expression in the brain lesions using PCR for quantitative assessment of TCRBV gene transcripts, together with size and sequence analysis of the third complementarity-determining region (CDR3) of the dominant TCR rearrangements. Restricted (oligoclonal) BV family usage was not observed, as all of the 22 BV PCR products were usually detected at levels exceeding the background. However, significant individual biases in the frequencies of different TCR families was evident. The distinct pattern of BV expression by infiltrating lymphocytes detected in the original PCR screening suggested a specific immune response. The primary structure of the rearranged CDR3 sequences for the BV family expressed at highest level in each sample was studied by size and sequence analysis. The data showed that predominant TCR BV families expressed in diseased brain tissue displayed limited size heterogeneity and extensive repetition of in-frame CDR3 nucleotide motifs. These findings demonstrate that the local immune response in Rasmussen's syndrome includes restricted T cell populations that have likely expanded from a few precursor T cells responding to discrete antigenic epitopes.

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