Disease relevance of Prss21

• When HEK293 cells were transformed by an expression plasmid carrying the entire protein-coding region of TESP5, the recombinant protein produced was released from the cell membrane by treatment with Bacillus cereus phosphatidylinositol-specific phospholipase C, indicating that TESP5 is glycosylphosphatidylinositol-anchored on the cell surface [1].
• The recently characterized human serine protease, Testisin, is expressed on premeiotic testicular germ cells and is a candidate type II tumor suppressor for testicular cancer [2].
• Our functional data coupled with the restricted normal tissue distribution of testisin and its overexpression in a majority of ovarian cancers validates this cell surface protein as a target for therapeutic intervention [3].

High impact information on Prss21

• Testisin, a glycosyl-phosphatidylinositol-linked serine protease, promotes malignant transformation in vitro and in vivo [3].
• Ectopic expression of testisin in a human ovarian cancer cell line without endogenous testisin expression, led to the formation of larger tumors in severe combined immunodeficient mice [3].
• Conversely, overexpression of testisin in an epithelial cell line induced colony formation in soft agar as well as s.c. tumor growth in severe combined immunodeficient mice [3].
• Small interfering RNA-mediated knockdown of endogenous testisin mRNA and protein expression in tumor cell lines led to increased apoptosis and diminished growth in soft agar [3].
• We first showed that testisin was localized on the surface of cultured tumor cells as a glycosyl-phosphatidylinositol-linked protein [3].

Biological context of Prss21

• 5'- and 3'-rapid amplification of cDNA ends approaches were carried out to deduce the nucleotide sequence of the full-length mT4 transcript [4].
• Tryptase 4, a new member of the chromosome 17 family of mouse serine proteases [4].
• Probing of GenBank's expressed sequence tag data base with these three tryptase cDNAs resulted in the identification of an expressed sequence tag that encodes a portion of a novel mouse serine protease (now designated mouse tryptase 4 (mT4) because it is the fourth member of this family) [4].
• In this study, we have PCR-amplified an EST clone encoding a testicular serine protease, termed TESP5, and then screened a mouse genomic DNA library using the DNA fragment as a probe [1].
• Enzymatic properties of recombinant TESP5 was similar to but distinguished from those of rat acrosin and pancreatic trypsin by the substrate specificity and inhibitory effects of serine protease inhibitors [1].

Anatomical context of Prss21

• As assessed by RNA blot, reverse transcriptase-polymerase chain reaction, and/or in situ hybridization analysis, mT4 is expressed in interleukin-5-dependent mouse eosinophils, as well as in ovaries and testes [4].
• Moreover, these two forms of TESP5 were selectively included into Triton X-100-insoluble microdomains, lipid rafts, of the sperm membranes [1].
• The observation that recombinant mT4 is preferentially retained in the endoplasmic reticulum of transiently transfected COS-7 cells suggests a convertase-like role for this integral membrane serine protease [4].
• Immunostaining for murine Testisin in mouse testis demonstrated specific staining in the cytoplasm and on the plasma membrane of round and elongating spermatids [2].
• Examination of murine Testisin mRNA expression in developing sperm confirmed that the onset of murine Testisin mRNA expression occurred at approximately day 18 after birth, corresponding to the appearance of spermatids in the testis, in contrast to the expression of human Testisin in spermatocytes [2].

Associations of Prss21 with chemical compounds

• A mouse serine protease TESP5 is selectively included into lipid rafts of sperm membrane presumably as a glycosylphosphatidylinositol-anchored protein [1].
• Due to its 17-mer hydrophobic domain at its C terminus, mT4 is a membrane-anchored tryptase more analogous to mTMT than the other members of its family [4].

Analytical, diagnostic and therapeutic context of Prss21

• We next explored the biological function of testisin in malignant transformation through manipulation of testisin expression in cell culture model systems [3].
• Using sequence analysis of bisulphite-treated genomic DNA, we find a strong relationship between hypermethylation of a 385 bp 5' CpG rich island of the Testisin gene, and silencing of the Testisin gene in a range of human tumour cell lines and in 100% (eight/eight) of testicular germ cell tumours [5].

References