Identification and characterization of a novel human testis-specific kinase substrate gene which is downregulated in testicular tumors

By using the positional candidate gene approach, we identified a novel puta tive serine/threonine kinase substrate gene that maps to chromosome 19q13.3 . Screening of expressed sequence tags and reverse transcription-polymerase chain reaction of total RNA from human tissues allowed us to establish the expression of the gene and delineate its genomic organization (GenBank Acc ession No. AF200923). This gene (TSKS, for testis-specific kinase substrate ) is composed of 11 exons and 10 intervening introns and is likely the huma n homolog of the mouse testis-specific serine kinase substrate gene, The pr edicted protein-coding region of the gene is 1779 bp, encoding for a 592-am ino-acid polypeptide with a calculated molecular mass of 65.1 kDa, Genomic analysis of the region 19q13.3 placed the TSKS gene close to the known gene s IRF3, RRAS, and alpha -Adaptin k TSKS exhibits high levels of expression exclusively in human testicular tissue, The expression of TSKS is downregul ated in cancerous testicular tissue, in comparison to adjacent normal tissu e, TSKS expression was very low or undetectable in seminoma, teratocarcinom a, embryonal, and Leydig cell tumors, while high expression was observed in testicular tissue adjacent to tumors which contain premalignant carcinoma in situ. The expression of the TSKS gene was very low in two human embryona l carcinoma cell lines, 2102Ep and NTERA-2. These observations suggest a ro le of TSKS in testicular physiology, most probably in the process of sperma togenesis or spermiogenesis. (C) 2001 Academic Press.