Isolation and Characterization of Two Novel Metalloproteinase Genes Linked to theCdc2LLocus on Human Chromosome 1p36.3

Gururajan, Rajagopal; Grenet, José; Lahti, Jill M.; Kidd, Vincent J.

doi:10.1006/geno.1998.5401

Cited by 62 publications

(41 citation statements)

References 24 publications

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“…Indirect evidence for a tumor-suppressive function of stromelysin-related proteases has been reported. 19 Alternatively, MMP-3 may be important only in very early phases of tumor initiation, as was suggested in studies of a murine mammary carcinoma model by Sternlicht et al 20 UPA activity also appears to decline in advanced, anaplastic primary tumors, although it appears substantially increased in metastatic LN deposits. These results suggest distinct roles for this plasminogen activator in the metastatic vs primary tumor growth process.…”

Section: Discussionmentioning

confidence: 94%

Patterns of protease production during prostate cancer progression: proteomic evidence for cascades in a transgenic model

Bok

Hansell²,

Nguyen³

et al. 2003

Prostate Cancer Prostatic Dis

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Extracellular proteases are recognized as critical factors in the progression of a number of carcinomas, including prostate cancer. Matrix metalloproteases (MMP) are important in processes of tumor growth, invasion and dissemination, but other classes of proteases, such as serine and cysteine proteases, also contribute. We utilized the TRAMP model for prostate cancer to elucidate proteases involved in prostate cancer progression. General proteomic analysis was performed on normal murine prostate, early TRAMP tumors and advanced TRAMP tumors, as well as normal and involved lymph nodes. Zymography and antigenic analyses revealed increased expression of mainly pro-MMP in early TRAMP tumors but substantial elaboration of activated MMP only in late TRAMP tumors. Progressive increase in cysteine, serine and certain membrane-bound proteases from normal to early to advanced prostate tumors, was also seen. Our results implicate pericellular proteases as initiators of major proteolytic cascades during tumor progression and suggest targets for maximal therapeutic effect.

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Section: Discussionmentioning

confidence: 94%

Patterns of protease production during prostate cancer progression: proteomic evidence for cascades in a transgenic model

Bok

Hansell²,

Nguyen³

et al. 2003

Prostate Cancer Prostatic Dis

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“…The construction of the microarray 20 and BAC/PAC clones used 12 have been published. Genomic DNA was isolated from lymphoblastoid cell lines established from four subjects (64,69,71,85) with known 1p36 rearrangements and from peripheral blood of a phenotypically normal male reference. Microarray analysis for subjects 30 and 40 was reported previously.…”

Section: Subjectsmentioning

confidence: 99%

“…68 MMP23A and its duplicated copy -B are located B0.5 -1.0 kb from the 3 0 end of the Cdc2L1-2 locus, which occupies B120 kb on 1p36.3. 69 The two copies of MMP23 share B90% sequence identity. Although MMP23 belongs to the metalloproteinase gene family, the gene does not fit into any of the subfamilies, instead being classified among several MMPs in the 'other MMPs' group.…”

Section: Mechanisms For Generating Complex Rearrangements Of Chromosomentioning

confidence: 99%

“…70 MMP23A and -B are expressed in numerous tissues, including placenta, ovary, testis, prostate, heart, and pancreas. 69,70 In addition, using gene expression analysis of hBMP2 injected in vivo into mouse quadriceps to induce bone formation, Clancy et al 31 showed increased expression of Mmp23 in osteoblasts and chrondrocytes, suggesting a role for Mmp23 in bone formation and remodeling.…”

Section: Mechanisms For Generating Complex Rearrangements Of Chromosomentioning

confidence: 99%

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Delineation of mechanisms and regions of dosage imbalance in complex rearrangements of 1p36 leads to a putative gene for regulation of cranial suture closure

Gajęcka

Ballif

et al. 2004

Eur J Hum Genet

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Structural chromosome abnormalities have aided in gene identification for over three decades. Delineation of the deletion sizes and rearrangements allows for phenotype/genotype correlations and ultimately assists in gene identification. In this report, we have delineated the precise rearrangements in four subjects with deletions, duplications, and/or triplications of 1p36 and compared the regions of imbalance to two cases recently published. Fluorescence in situ hybridization (FISH) analysis revealed the size, order, and orientation of the duplicated/triplicated segments in each subject. We propose a premeiotic model for the formation of these complex rearrangements in the four newly ascertained subjects, whereby a deleted chromosome 1 undergoes a combination of multiple breakage-fusion-bridge (BFB) cycles and inversions to produce a chromosome arm with a complex rearrangement of deleted, duplicated and triplicated segments. In addition, comparing the six subjects' rearrangements revealed a region of overlap that when triplicated is associated with craniosynostosis and when deleted is associated with large, late-closing anterior fontanels. Within this region are the MMP23A and -B genes. We show MMP23 gene expression at the cranial sutures and we propose that haploinsufficiency results in large, late-closing anterior fontanels and overexpression results in craniosynostosis. These data emphasize the important role of cytogenetics in investigating and uncovering the etiologies of human genetic disease, particularly cytogenetic imbalances that reveal potentially dosage-sensitive genes.

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“…The function of the proline-rich linker peptide that connects the catalytic and the hemopexin domains is not known, although its interaction with triple helical collagen is hypothesized based on molecular modeling (22). MMP-23 has cysteine-rich, proline-rich, and IL-1 receptor-like regions instead of the hemopexin domain (10). A transmembrane domain is found in the MT-MMPs, which anchors those enzymes to the cell surface.…”

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confidence: 99%

Matrix Metalloproteinases

Nagase¹,

Woessner²

1999

Journal of Biological Chemistry

3,811

2,840

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The timely breakdown of extracellular matrix (ECM) 1 is essential for embryonic development, morphogenesis, reproduction, and tissue resorption and remodeling. The matrix metalloproteinases (MMPs), also called matrixins, are thought to play a central role in these processes. The expression of most matrixins is transcriptionally regulated by growth factors, hormones, cytokines, and cellular transformation (1, 2). The proteolytic activities of MMPs are precisely controlled during activation from their precursors and inhibition by endogenous inhibitors, ␣-macroglobulins, and tissue inhibitors of metalloproteinases (TIMPs). Table I lists currently known vertebrate matrixins. In addition, non-vertebrate members have been identified in sea urchins (3), Caenorhabditis elegans (4), soybean (5), and Arabidopsis thaliana (6). Most of these MMPs are the subject of individual chapters in the Handbook of Proteolytic Enzymes (7). This minireview focuses on recent progress in regulation of matrixin activities and their biological and pathological implications. Domain Structure and FunctionAll matrixins are synthesized as prepro-enzymes and secreted as inactive pro-MMPs in most cases. The primary structures of 20 vertebrate matrixins comprise several domain motifs, as illustrated in Fig. 1; the domain composition for each MMP is listed in Table I.The propeptide domain (about 80 amino acids) has a conserved unique PRCG(V/N)PD sequence. The Cys within this sequence (the "cysteine switch") ligates the catalytic zinc to maintain the latency of pro-MMPs (8, 9). This sequence is missing in MMP-23 (10). Stromelysin 3 (MMP-11), MT-MMPs, Xenopus MMP, and MMP-23 have a proprotein processing sequence RX(K/R)R at the C-terminal end of the propeptide, and MMP-11 (11) and MMP-14 (12) were shown to be activated intracellularly by furin.The catalytic domain (about 170 amino acids) contains a zinc binding motif HEXXHXXGXXH and a conserved methionine, which forms a unique "Met-turn" structure (13). This domain consists of a five-stranded ␤-sheet, three ␣-helices, and bridging loops (14). These backbone structures including the "Met-turn" are similar to those of the members from other metalloproteinase families, i.e. astacins, reprolysins (ADAMs), and serralysins; these four families constitute the "metzincins" (13). The catalytic domains of matrixins have an additional structural zinc ion and 2-3 calcium ions, which are required for the stability and the expression of enzymic activity. MMP-2 and MMP-9 have three repeats of fibronectin-type II domain inserted in the catalytic domain. These repeats interact with collagens and gelatins (15, 16).The C-terminal hemopexin-like domain (about 210 amino acids) has an ellipsoidal disk shape with a four bladed ␤-propeller structure; each blade consists of four antiparallel ␤-strands and an ␣-helix (17). The hemopexin domain is an absolute requirement for collagenases to cleave triple helical interstitial collagens (18), although the catalytic domains alone retain proteolytic activity toward other substra...

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Isolation and Characterization of Two Novel Metalloproteinase Genes Linked to theCdc2LLocus on Human Chromosome 1p36.3

Cited by 62 publications

References 24 publications

Patterns of protease production during prostate cancer progression: proteomic evidence for cascades in a transgenic model

Patterns of protease production during prostate cancer progression: proteomic evidence for cascades in a transgenic model

Delineation of mechanisms and regions of dosage imbalance in complex rearrangements of 1p36 leads to a putative gene for regulation of cranial suture closure

Matrix Metalloproteinases

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