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 putative 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 Accession No. AF200923). This gene (TSKS, for testis-specific kinase substrate) is composed of 11 exons and 10 intervening introns and is likely the human homolog of the mouse testis-specific serine kinase substrate gene. The predicted protein-coding region of the gene is 1779 bp, encoding for a 592-amino-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 genes IRF3, RRAS, and alpha-Adaptin A. TSKS exhibits high levels of expression exclusively in human testicular tissue. The expression of TSKS is downregulated in cancerous testicular tissue, in comparison to adjacent normal tissue. TSKS expression was very low or undetectable in seminoma, teratocarcinoma, 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 embryonal carcinoma cell lines, 2102Ep and NTERA-2. These observations suggest a role of TSKS in testicular physiology, most probably in the process of spermatogenesis or spermiogenesis.
Scorilas
A
A
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
Yousef
G M
GM
Jung
K
K
Rajpert-De Meyts
E
E
Carsten
S
S
Diamandis
E P
EP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002278:Carcinoma in Situ / Q000235:genetics; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D003598:Cytoskeletal Proteins; D005091:Exons; D020224:Expressed Sequence Tags; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007438:Introns; D007984:Leydig Cell Tumor / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009928:Organ Specificity; D010750:Phosphoproteins; D011230:Precancerous Conditions / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018239:Seminoma / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013724:Teratoma / Q000235:genetics; D013736:Testicular Neoplasms / Q000235:genetics* / Q000378:metabolism; D013737:Testis / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D011506:Proteins; C432423:TSKS protein, human; D017346:Protein Serine-Threonine Kinases