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Testisin is a recently identified human serine protease expressed by premeiotic testicular germ cells and is a candidate tumor suppressor for testicular cancer. Here, we report the characterization of the gene encoding testisin, designated PRSS21, and its localization on the short arm of human chromosome 16 (16p13.3) between the microsatellite marker D16S246 and the radiation hybrid breakpoint CY23HA. We have further refined the localization to cosmid 406D6 in this interval and have established that the gene is approximately 4. 5 kb in length, and contains six exons and five intervening introns. The structure of PRSS21 is very similar to the human prostasin gene (PRSS8) which maps nearby on 16p11.2, suggesting that these genes may have evolved through gene duplication. Sequence analysis showed that the two known isoforms of testisin are generated by alternative pre-mRNA splicing. A major transcription initiation site was identified 97 nucleotides upstream of the testisin translation start and conforms to a consensus initiator element. The region surrounding the transcription initiation site lacks a TATA consensus sequence, but contains a CCAAT sequence and includes a CpG island. The 5'-flanking region contains several consensus response elements including Sp1, AP1 and several testis-specific elements. Analysis of testisin gene expression in tumor cell lines shows that testisin is not expressed in testicular tumor cells but is aberrantly expressed in some tumor cell lines of non-testis origin. These data provide the basis for identifying potential genetic alterations of PRSS21 that may underlie both testicular abnormalities and tumorigenesis.

Type

Journal article

Journal

Biochim Biophys Acta

Publication Date

2000

Volume

1492

Pages

63 - 71

Keywords

Alternative Splicing Amino Acid Sequence Base Sequence *Chromosome Mapping *Chromosomes, Human, Pair 16 Cosmids/genetics DNA/analysis DNA, Complementary/metabolism *Gene Expression Regulation, Enzymologic Genes, Regulator/genetics Genetic Vectors Genome, Human Human Male Molecular Sequence Data Promoter Regions (Genetics)/genetics Protein Isoforms/genetics RNA Precursors/metabolism Serine Endopeptidases/biosynthesis/*genetics/metabolism Support, Non-U.S. Gov't Transcription, Genetic Transfection Tumor Cells, Cultured