Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Promatrilysin expressed in Escherichia coli and Chinese hamster ovary cells contains 2.36 +/- 0.19 and 2.13 +/- 0.39 moles of zinc per mole of protein, respectively, while the activated enzyme contains 2.22 +/- 0.21. The catalytic domain of stromelysin-1 expressed in E. coli contains 2.22 +/- 0.11. Thus these matrix metalloproteinases contain two metal binding sites at which zinc is bound firmly and possibly a third site at which it is bound weakly. Promatrilysin and matrilysin do not contain significant amounts of Fe, Cu, Mn, or Ni. All known matrix metalloproteinases have a sequence homologous to the zinc binding site of astacin, HExxHxxGxxH, suggesting that one of the zinc sites is catalytic in agreement with the known inhibition of these enzymes by chelators.
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PMID:Zinc content of promatrilysin, matrilysin and the stromelysin catalytic domain. 800 31

Expression of MMP-2 in melanoma cells has been demonstrated to be involved in the degradation of extracellular matrix during melanoma growth and to correlate with later melanoma metastasis. MMP-2 is considered to be activated by membrane-associated matrix metalloproteinases (MT-MMPs). To know whether MT-MMPs are involved in the activation of MMP-2 in melanoma cells, immunohistochemical studies were performed in primary and metastatic melanoma by use of the antibodies for MT1-MMP, MT2-MMP and MT3-MMP. Expression of MT1-MMP, MT2-MMP, MT3-MMP and MMP-2 in nevocellular nevus (n = 5), dysplastic nevus (n = 2) and juvenile melanoma (n = 3) was undetectable or detected in only a few cells. Superficial spreading melanoma (SSM) (n = 3) and acral lentiginous melanoma (ALM) (n = 3) showed a moderate expression of MT1 approximately 3-MMP. In nodular melanoma (NM) (n = 2) and metastatic melanoma (n = 3), MT1 approximately 3-MMP was more intensely expressed. Double immunofluorescence demonstrated a consistent colocalization of MT2-MMP/MMP-2 and MT3-MMP/MMP-2 in the NM and metastatic melanoma cells. The colocalization of MT2,3-MMP and MMP-2 in nodular and metastatic melanoma cells suggests that MT-MMPs and MMP-2 co-operate in the invasive and metastatic process of melanoma cells.
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PMID:Coordinate expression of membrane type-matrix metalloproteinases-2 and 3 (MT2-MMP and MT3-MMP) and matrix metalloproteinase-2 (MMP-2) in primary and metastatic melanoma cells. 1152 48

Metastatic melanoma remains the deadliest of all skin cancers with a survival rate at five years of less than 15%. MT1-MMP is a membrane-associated matrix metalloproteinase that controls pericellular proteolysis and is an important, invasion-promoting, pro-tumorigenic MMP in cancer. We show that deregulation of MT1-MMP expression happens as early as the transition from nevus to primary melanoma and continues to increase during melanoma progression. Furthermore, MT1-MMP expression is associated with poor melanoma patient outcome, underscoring a pivotal role of MT1-MMP in melanoma pathogenesis. We demonstrate that MT1-MMP is directly required for melanoma cells to metastasize, as cells deprived of MT1-MMP fail to form distant metastasis in an orthotopic mouse melanoma model. We show that MT1-MMP affects cell invasion by activating its target MMP2. Importantly, we demonstrate, for the first time, that activation of MMP2 by MT1-MMP is required to sustain RAC1 activity and promote MT1-MMP-dependent cell motility. These data highlight a novel MT1-MMP/MMP2/RAC1 signaling axis in melanoma that may represent an intriguing molecular target for the treatment of invasive melanoma.
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PMID:MT1-MMP modulates melanoma cell dissemination and metastasis through activation of MMP2 and RAC1. 2438 69