Molecular characterization of zyme/protease M/neurosin (PRSS9), a hormonally regulated kallikrein-like serine protease.

The cDNA for the zyme/protease M/neurosin gene (HGMW-approved symbol PRSS9) has recently been identified. Zyme appears to play a role in Alzheimer disease as well as in breast cancer. In this paper, we describe the complete genomic organization of the zyme gene. Zyme spans 10.5 kb of genomic sequence on chromosome 19q13.3-q13.4. The gene consists of seven exons, the first two of which are untranslated. All splice junctions follow the GT/AG rule, and the intron phases are identical to those of many other genes belonging to the same family, i.e., the kallikreins, NES1, and neuropsin. Fine-mapping of the genomic locus indicates that zyme lies upstream of the NES1 gene and downstream from the PSA and KLK2 genes. Tissue expression studies indicate that zyme is expressed mainly in brain tissue, including spinal cord and cerebellum, in mammary gland, and in kidney and uterus. Zyme is regulated by steroid hormones in the breast carcinoma cell line BT-474. Estrogens and progestins, and to a lesser extent androgens, up-regulate the zyme gene in a dose-dependent manner.

[1]  L. Secker-Walker.  Catalog of Chromosome Aberrations in Cancer , 1996, British Journal of Cancer.

[2]  D. Wazer,et al.  Identification of a novel serine protease-like gene, the expression of which is down-regulated during breast cancer progression. , 1996, Cancer research.

[3]  Eric D. Green,et al.  Genome analysis : a laboratory manual , 1997 .

[4]  E. Diamandis,et al.  Salivary duct carcinoma secreting prostate-specific antigen. , 1996, American journal of clinical pathology.

[5]  S. G. Farmer.  The Kinin System , 1997 .

[6]  P. Riegman,et al.  Characterization of the human kallikrein locus. , 1992, Genomics.

[7]  E. Diamandis,et al.  Prostate-specific antigen levels in nipple aspirate fluid correlate with breast cancer risk. , 1996, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[8]  G. Sutherland,et al.  Structure and chromosomal localization of the human renal kallikrein gene. , 1988, Biochemistry.

[9]  C. J. Roberts,et al.  Expression of herpes virus thymidine kinase in Neurospora crassa. , 1997, Nucleic acids research.

[10]  H. Lilja,et al.  Activation of the zymogen form of prostate-specific antigen by human glandular kallikrein 2. , 1997, Biochemical and biophysical research communications.

[11]  R. Richards,et al.  Mouse glandular kallikrein genes. Identification, structure, and expression of the renal kallikrein gene. , 1986, The Journal of biological chemistry.

[12]  P. Riegman,et al.  Characterization of the prostate-specific antigen gene: a novel human kallikrein-like gene. , 1989, Biochemical and biophysical research communications.

[13]  M. Schachter.  Kallikreins (kininogenases)--a group of serine proteases with bioregulatory actions. , 1979, Pharmacological reviews.

[14]  P. Sismondi,et al.  Prostate-specific antigen is a new favorable prognostic indicator for women with breast cancer. , 1995, Cancer research.

[15]  B. Morris,et al.  Kallikrein and renin: molecular biology and biosynthesis. , 1981, Clinical science.

[16]  D. Wazer,et al.  The role for NES1 serine protease as a novel tumor suppressor. , 1998, Cancer research.

[17]  S. Yoshida,et al.  Sequence analysis and expression of human neuropsin cDNA and gene. , 1998, Gene.

[18]  B. Vogelstein,et al.  Preparative and analytical purification of DNA from agarose. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[19]  James R. Miller,et al.  Zyme, a Novel and Potentially Amyloidogenic Enzyme cDNA Isolated from Alzheimer’s Disease Brain* , 1997, The Journal of Biological Chemistry.

[20]  E. Diamandis,et al.  Prognostic value of prostate-specific antigen for women with breast cancer: a large United States cohort study. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[21]  M. Pericak-Vance,et al.  Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. , 1991, American journal of human genetics.

[22]  C. López-Otín,et al.  Human glandular kallikrein in breast milk, amniotic fluid, and breast cyst fluid. , 1999, Clinical chemistry.

[23]  J. Clements.  The Molecular Biology of the Kallikreins and their Roles in Inflammation , 1997 .

[24]  M. O. Dayhoff,et al.  Atlas of protein sequence and structure , 1965 .

[25]  W. Gerald,et al.  Immunological identification of rat tissue kallikrein cDNA and characterization of the kallikrein gene family. , 1986, Biochimica et biophysica acta.

[26]  R. MacGillivray,et al.  Structure and evolution of the bovine prothrombin gene. , 1988, Journal of molecular biology.

[27]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[28]  Yôichi Iida,et al.  Quantification analysis of 5'-splice signal sequences in mRNA precursors. Mutations in 5'-splice signal sequence of human β-globin gene and β-thalassemia , 1990 .

[29]  R. Richards,et al.  Genes for the alpha and gamma subunits of mouse nerve growth factor are contiguous. , 1985, The EMBO journal.

[30]  S. Scherer,et al.  Structural characterization and mapping of the normal epithelial cell-specific 1 gene. , 1998, Biochemical and biophysical research communications.

[31]  R. Richards,et al.  Mouse glandular kallikrein genes. Structure and partial sequence analysis of the kallikrein gene locus. , 1987, The Journal of biological chemistry.

[32]  B. Morris,et al.  Mouse glandular kallikrein genes. Nucleotide sequence of cloned cDNA coding for a member of the kallikrein arginyl esteropeptidase group of serine proteases. , 1982, The Journal of biological chemistry.

[33]  G. Reifenberger,et al.  Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. , 1994, The American journal of pathology.

[34]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[35]  G. Yousef,et al.  Identification of novel human kallikrein-like genes on chromosome 19q13.3-q13.4. , 1999, Anticancer research.

[36]  T. Tanaka,et al.  Molecular cloning of a novel trypsin-like serine protease (neurosin) preferentially expressed in brain. , 1997, Biochimica et biophysica acta.

[37]  S. Mok,et al.  A Novel Protease Homolog Differentially Expressed in Breast and Ovarian Cancer , 1996, Molecular medicine.

[38]  F. Mitelman,et al.  Catalog of Chromosome Aberrations in Cancer , 1996, British Journal of Cancer.

[39]  B. Morris,et al.  Primary structure of a human glandular kallikrein gene. , 1987, DNA.

[40]  T. Lennard,et al.  Prostate‐specific antigen in breast cyst fluid: Possible role of prostate‐specific antigen in hormone‐dependent breast cancer , 1996 .

[41]  E. Diamandis,et al.  Detection of prostate-specific antigen mRNA and protein in breast tumors. , 1996, Clinical chemistry.