The Human Cysteine‐Rich Secretory Protein (CRISP) Family

Abstract

We report the isolation and characterisation of cDNAs encoding three different, human members of the cysteine-rich secretory protein (CRISP) family. The novel CRISP-I exists in five cDNA subtypes differing by the presence or absence of a stretch coding for a C-terminal cysteine-rich domain so far found in all members of the family, and by the length of their 3'-untranslated region. CRISP-2 cDNA corresponds to the previously described TPXI form, with so far unreported 5'-untranslated sequence heterogeneities while CRISP-3 cDNA codes for a new, unique protein. Northern blot analysis of various human organs indicates that CRISP-1 transcripts are epididymis-specific whereas CRISP-2ITPXI transcripts are detected mainly in the testis and also in the epididymis. CRISP-3 transcripts are more widely distributed and found predominantly in the salivary gland, pancreas and prostate, and in less abundance in the epididymis, ovary, thymus and colon. A protein reacting with an anti-mouse CRISP-I antibody was isolated from human epididymal extracts and N-terminal sequencing revealed that it corresponded to the CRISP-I cDNA we have isolated. In contrast to findings on its rat counterpart epididymal protein DE/acidjc epididymal glycoprotein (AEG), no significant association of CRISP-1 with human spermatozoa was observed.

Cysteine‐rich secretory proteins are not exclusively expressed in the male reproductive tract

“…As evidenced by Northern blotting, Crisp2 is most abundantly expressed in the testis (Kasahara et al, 1989;Kratzschmar et al, 1996;O'Bryan et al, 1998). Crisp2 is not regulated by androgens and its mRNA is first expressed in pachytene spermatocytes (Haendler et al, 1997;O'Bryan et al, 1998).…”

“…The mechanism of this potential activity is currently unknown, but the addition of peptides corresponding to the CAP domain signature motifs and cell transfection experiments using truncated forms of CRISP2 suggest that there is a CAP protein involved in sperm-oocyte binding via the CAP domain (Maeda et al, 1999;Ellerman et al, 2006). Northern blotting data from several species shows that Crisp1 is most abundantly expressed in the epididymis (Charest et al, 1989;Haendler et al, 1993;Kratzschmar et al, 1996).…”

“…Crisp3 was initially identified in the mouse salivary gland (Haendler et al, 1993) and later in the human as SGP28 (Kjeldsen et al, 1996). Subsequently, it was identified in human prostate (Kratzschmar et al, 1996) where it appears promising as a marker of prostate cancer (Kosari et al, 2002;Bjartell et al, 2006Bjartell et al, , 2007 and in the salivary glands where it appears promising as a marker for Sjögren's syndrome (Tapinos et al, 2002;Laine et al, 2007). The mechanism by which CRISP3 is involved in these pathological processes is currently unknown.…”

“…The mechanism by which CRISP3 is involved in these pathological processes is currently unknown. It has been suggested that CRISP3 (and indeed other CRISPs) may have a role in innate immunity by virtue of their presence in exocrine secretions, e.g., in saliva and tears, and in immune cells, e.g., in pre-B lymphocytes and neutrophils (Haendler et al, 1993(Haendler et al, , 1999Kjeldsen et al, 1996;Kratzschmar et al, 1996;Pfisterer et al, 1996). CRISP4 was only recently identified and it was at this time that the extent of confusion in naming between species became clear (Jalkanen et al, 2005;Nolan et al, 2006).…”

Cysteine-rich secretory protein 3 overexpression is linked to a subset of PTEN-deleted ERG fusion-positive prostate cancers with early biochemical recurrence

“…CRISP3 is expressed at low levels in normal human prostate and strongly upregulated in a fraction of prostate cancers. [3][4][5][6] The clinical relevance of CRISP3 overexpression is controversially discussed. Some studies found CRISP3 overexpression to be associated with increased risk of tumor recurrence, 7 unfavorable tumor phenotype, 8,9 castration-resistant prostate cancer, and metastasis, 9,10 whereas others could not find any clinically relevant associations.…”