Matrix Metalloproteinase Function
Published by Anonymous on 2007/9/24 (2390 reads)
1: Cell Death Differ. 2007 Jul;14(7):1255-8. Epub 2007 Apr 13.
Matrix metalloproteinase-9 in glutamate-dependent adult brain function and dysfunction.
Michaluk P, Kaczmarek L.
Laboratory for Molecular Neurobiology, Nencki Institute, 02-093 Warsaw, Pasteura 3, Poland.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 17431423 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
2: Biochimie. 2005 Mar-Apr;87(3-4):369-76.
Regulation of matrix metalloproteinase (MMP) activity by the low-density lipoprotein receptor-related protein (LRP). A new function for an "old friend".
Emonard H, Bellon G, de Diesbach P, Mettlen M, Hornebeck W, Courtoy PJ.
CNRS UMR 6198, IFR 53, Faculté de Médecine, 51, rue Cognacq Jay, 51095 Reims cedex, France. herve.emonard@univ-reims.fr
Matrix metalloproteinases (MMPs) are essential contributors to a microenvironment that promotes tumour progression. During the two last decades, inhibition of MMPs has become the focus of considerable interest for cancer therapy, and numerous synthetic metalloproteinase inhibitors have been developed by the pharmaceutical industry. However, clinical trials have shown disappointing efficacy or unexpected toxicity and new targets are thus eagerly awaited. The identification of endocytic clearance of several MMPs by the low-density lipoprotein receptor-related protein (LRP) might provide insight into novel strategies for controlling MMP level during malignant processes. This review attempts to summarize recent aspects on the cellular and molecular basis of LRP-mediated endocytic disposal of MMPs.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 15781324 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
3: Biochem Soc Symp. 2003;(70):1-14.
Structural basis of matrix metalloproteinase function.
Bode W.
Max-Planck-Institut für Biochemie, D-82152 Martinsried, Germany. bode@biochem.mpg.de
The matrix metalloproteinases (MMPs) constitute a family of multidomain zinc endopeptidases which contain a catalytic domain with a common metzincin-like topology. The MMPs are involved not only in extracellular matrix degradation, but also in a number of other biological processes. Normally, their proteolytic activity is regulated precisely by their main endogenous protein inhibitors, in particular the tissue inhibitors of metalloproteinases (TIMPs). Disruption of this balance results in serious diseases, such as arthritis, tumour growth and metastasis, rendering the MMPs attractive targets for inhibition therapy. Knowledge of their tertiary structures is crucial for a full understanding of their functional properties. Since the first publication of atomic MMP structures in 1994, much more structural information has become available on details of the catalytic domain, on its interaction with synthetic and protein inhibitors, on domain organization and on the formation of complexes with other proteins. This review will outline our current knowledge of MMP structure.
Publication Types:
Review
PMID: 14587278 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
4: Curr Top Dev Biol. 2003;54:371-89.
Emmprin (CD147), a cell surface regulator of matrix metalloproteinase production and function.
Toole BP.
Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Publication Types:
Review
PMID: 12696756 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
5: Crit Rev Biochem Mol Biol. 2002;37(3):149-66.
The structure, regulation, and function of human matrix metalloproteinase-13.
Leeman MF, Curran S, Murray GI.
Department of Pathology, University of Aberdeen, Foresterhill, UK.
Matrix metalloproteinase-13 (MMP-13) is a proteolytic enzyme that belongs to a large family of extracellular matrix-degrading endopeptidases that are characterized by a zinc-binding motif at their catalytic sites. MMP-13 has a key role in the MMP activation cascade and appears to be critical in bone metabolism and homeostasis. It also has an important role in tumor invasion and metastasis. This commentary provides a detailed overview of the regulatory mechanisms, structure, and function of human MMP-13 and highlights the key factors involved in the biology of this important molecule.
Publication Types:
Review
PMID: 12139441 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
6: Ann N Y Acad Sci. 2000 May;902:27-37; discussion 37-8.
Genetic diversity in the matrix metalloproteinase family. Effects on function and disease progression.
Henney AM, Ye S, Zhang B, Jormsjö S, Whatling C, Eriksson P, Hamsten A.
King Gustav Vth Research Institute, Karolinska Institute, Stockholm, Sweden. adriano.henney@astrazeneca.com
Atherosclerosis is an example of a complex trait, where the course of the disease is influenced by a combination of common variation in a constellation of genes and the effect of a wide range of environmental variables. Thus, the underlying disease mechanisms will be modulated by genetic diversity and the effect this diversity has on an individual's response to environmental challenges such as smoking, diet, and exercise. Unlike the consequences of mutations in severe single-gene disorders on protein function, the impact of individual common, functionally important sequence changes in genes contributing to multifactorial diseases is likely to be very small. The challenge is to dissect the contribution that each of these genes makes to the disease process. We have tackled this by identifying common genetic variants, studying their effects on function, and applying them to the analysis of association in appropriately structured and suitably powered studies. Even with our incomplete understanding of the disease, the list of potential candidate genes we could study is vast; but, we do know from pathological studies that a wide spectrum of structural architecture exists in atherosclerotic plaques, suggesting that remodeling of vascular connective tissue is fundamentally important. Matrix remodeling is controlled by a complex network of cell and matrix interactions, the net outcome of which is the product of a balance between synthetic and degradative processes. Our work has focused on the family of enzymes and inhibitors most directly associated with matrix turnover--the matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs, tissue inhibitors of MPs). We specifically searched for functionally relevant genetic variants that might modulate the delicate control of matrix turnover. Using these molecular genetic strategies to investigate the impact of natural genetic variation on vascular matrix remodeling has begun to shed new light on the importance of these genes in atherogenesis.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 10865823 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
7: Matrix Biol. 1997 Mar;15(8-9):527-33.
Mighty mice: transgenic technology "knocks out" questions of matrix metalloproteinase function.
Shapiro SD.
Department of Medicine, Washington University School of Medicine, Barnes Jewish Hospital, St. Louis, Missouri, USA.
Matrix metalloproteinases (MMP) comprise a family of structurally related proteinases that are believed to play a critical role in many physiological and pathological processes. Transgenic technology offers the possibility of determining whether MMPs contribute directly to these processes. For example, gain of function and loss of function models have confirmed causative roles of MMPs in the development of pulmonary emphysema and unexpectedly uncovered an MMP-dependent mechanism of inflammatory cell recruitment. Limitations of these techniques and powerful applications on the horizon are also presented as we embark on an era where controlled experiments can be performed in complex mammalian models.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 9138285 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
8: Matrix Biol. 1997 Mar;15(8-9):511-8.
Relating matrix metalloproteinase structure to function: why the "hemopexin" domain?
Murphy G, Knäuper V.
Strangeways Research Laboratory, Cambridge, United Kingdom.
Matrix metalloproteinases are thought to be key players in the remodelling activity of cells associated with both physiological and pathological processes. They share a relatively conserved structure with a number of identifiable modules linked to their specific functions. The structure of the individual domains of a number of matrix metalloproteinases have now been elucidated. Here we review these data in the light of complementary studies on the behaviour of these enzymes in biological systems. In particular we focus on the C-terminal hemopexin-like domain which has intriguingly specific roles in individual matrix metalloproteinases.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 9138283 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
9: Enzyme Protein. 1996;49(1-3):38-58.
What structure and function of avian plasminogen activator and matrix metalloproteinase-2 reveal about their counterpart mammalian enzymes, their regulation and their role in tumor invasion.
Alexander DS, Aimes RT, Quigley JP.
Department of Cellular and Molecular Pathology, SUNY at Stony Brook 11794-8691, USA.
Rous sarcoma virus-transformed chick embryo fibroblasts (RSVCEF) constitute a well-characterized model system for oncogenic transformation, matrix degradation, and cancer invasion. As RSVCEF cultures employ both serine protease and metalloprotease cascades in the process of matrix degradation, they have contributed significantly to understanding the nature and regulation of these molecules involved in invasive cell behavior. RSVCEF produce elevated levels of a matrix metalloprotease-2 (MMP-2) whose hemopexin domain differs from mammalian MMP-2. The majority of MMP-2 produced by RSVCEF is present in a TIMP-free form which enhances its activation, catalytic activity and substrate specificity and therefore its matrix-degrading ability. RSVCEFs also exhibit high levels of urokinase-type plasminogen activator (uPA), which is found in active form in their conditioned medium in complete absence of plasminogen. Recombinantly expressed avian uPA is also in active form, while an active-site mutant of the same maintains its zymogen form, indicating the mechanism of activation of chicken uPA is autocatalytic. A domain and sequence comparison between chicken and human uPA attempts to identify motifs potentially responsible for the zymogen instability of avian uPA and its capability to autoactivate.
Publication Types:
Review
PMID: 8796996 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
10: Immun Infekt. 1993 Apr;21 Suppl 1:20-1.
[The matrix metalloproteinase gene family: structure, function, expression, and role in destructive joint disease]
[Article in German]
Conca W.
Abteilung Rheumatologie und Klinische Immunologie, Medizinische Universitätsklinik Freiburg.
The matrix metalloproteinases, i.e. collagenases, gelatinases and stromelysins, are members of a gene family. They are capable of degrading every component of the extracellular matrix. Tissue destruction observed in inflammatory joint disease is largely accounted for by the action of these enzymes. Among the most potent inducers of metalloproteinase expression are the inflammatory cytokines IL-1 and TNF-alpha. Studies of mechanisms of induction by these mediators at the transcriptional level have improved our understanding of the biological controls of metalloproteinase synthesis. Cytokine inhibitors might serve to inhibit or postpone the crippling consequences of metalloproteinase action.
Publication Types:
English Abstract
Review
PMID: 8344678 [PubMed - indexed for MEDLINE]
Matrix metalloproteinase-9 in glutamate-dependent adult brain function and dysfunction.
Michaluk P, Kaczmarek L.
Laboratory for Molecular Neurobiology, Nencki Institute, 02-093 Warsaw, Pasteura 3, Poland.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 17431423 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
2: Biochimie. 2005 Mar-Apr;87(3-4):369-76.
Regulation of matrix metalloproteinase (MMP) activity by the low-density lipoprotein receptor-related protein (LRP). A new function for an "old friend".
Emonard H, Bellon G, de Diesbach P, Mettlen M, Hornebeck W, Courtoy PJ.
CNRS UMR 6198, IFR 53, Faculté de Médecine, 51, rue Cognacq Jay, 51095 Reims cedex, France. herve.emonard@univ-reims.fr
Matrix metalloproteinases (MMPs) are essential contributors to a microenvironment that promotes tumour progression. During the two last decades, inhibition of MMPs has become the focus of considerable interest for cancer therapy, and numerous synthetic metalloproteinase inhibitors have been developed by the pharmaceutical industry. However, clinical trials have shown disappointing efficacy or unexpected toxicity and new targets are thus eagerly awaited. The identification of endocytic clearance of several MMPs by the low-density lipoprotein receptor-related protein (LRP) might provide insight into novel strategies for controlling MMP level during malignant processes. This review attempts to summarize recent aspects on the cellular and molecular basis of LRP-mediated endocytic disposal of MMPs.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 15781324 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
3: Biochem Soc Symp. 2003;(70):1-14.
Structural basis of matrix metalloproteinase function.
Bode W.
Max-Planck-Institut für Biochemie, D-82152 Martinsried, Germany. bode@biochem.mpg.de
The matrix metalloproteinases (MMPs) constitute a family of multidomain zinc endopeptidases which contain a catalytic domain with a common metzincin-like topology. The MMPs are involved not only in extracellular matrix degradation, but also in a number of other biological processes. Normally, their proteolytic activity is regulated precisely by their main endogenous protein inhibitors, in particular the tissue inhibitors of metalloproteinases (TIMPs). Disruption of this balance results in serious diseases, such as arthritis, tumour growth and metastasis, rendering the MMPs attractive targets for inhibition therapy. Knowledge of their tertiary structures is crucial for a full understanding of their functional properties. Since the first publication of atomic MMP structures in 1994, much more structural information has become available on details of the catalytic domain, on its interaction with synthetic and protein inhibitors, on domain organization and on the formation of complexes with other proteins. This review will outline our current knowledge of MMP structure.
Publication Types:
Review
PMID: 14587278 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
4: Curr Top Dev Biol. 2003;54:371-89.
Emmprin (CD147), a cell surface regulator of matrix metalloproteinase production and function.
Toole BP.
Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Publication Types:
Review
PMID: 12696756 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
5: Crit Rev Biochem Mol Biol. 2002;37(3):149-66.
The structure, regulation, and function of human matrix metalloproteinase-13.
Leeman MF, Curran S, Murray GI.
Department of Pathology, University of Aberdeen, Foresterhill, UK.
Matrix metalloproteinase-13 (MMP-13) is a proteolytic enzyme that belongs to a large family of extracellular matrix-degrading endopeptidases that are characterized by a zinc-binding motif at their catalytic sites. MMP-13 has a key role in the MMP activation cascade and appears to be critical in bone metabolism and homeostasis. It also has an important role in tumor invasion and metastasis. This commentary provides a detailed overview of the regulatory mechanisms, structure, and function of human MMP-13 and highlights the key factors involved in the biology of this important molecule.
Publication Types:
Review
PMID: 12139441 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
6: Ann N Y Acad Sci. 2000 May;902:27-37; discussion 37-8.
Genetic diversity in the matrix metalloproteinase family. Effects on function and disease progression.
Henney AM, Ye S, Zhang B, Jormsjö S, Whatling C, Eriksson P, Hamsten A.
King Gustav Vth Research Institute, Karolinska Institute, Stockholm, Sweden. adriano.henney@astrazeneca.com
Atherosclerosis is an example of a complex trait, where the course of the disease is influenced by a combination of common variation in a constellation of genes and the effect of a wide range of environmental variables. Thus, the underlying disease mechanisms will be modulated by genetic diversity and the effect this diversity has on an individual's response to environmental challenges such as smoking, diet, and exercise. Unlike the consequences of mutations in severe single-gene disorders on protein function, the impact of individual common, functionally important sequence changes in genes contributing to multifactorial diseases is likely to be very small. The challenge is to dissect the contribution that each of these genes makes to the disease process. We have tackled this by identifying common genetic variants, studying their effects on function, and applying them to the analysis of association in appropriately structured and suitably powered studies. Even with our incomplete understanding of the disease, the list of potential candidate genes we could study is vast; but, we do know from pathological studies that a wide spectrum of structural architecture exists in atherosclerotic plaques, suggesting that remodeling of vascular connective tissue is fundamentally important. Matrix remodeling is controlled by a complex network of cell and matrix interactions, the net outcome of which is the product of a balance between synthetic and degradative processes. Our work has focused on the family of enzymes and inhibitors most directly associated with matrix turnover--the matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs, tissue inhibitors of MPs). We specifically searched for functionally relevant genetic variants that might modulate the delicate control of matrix turnover. Using these molecular genetic strategies to investigate the impact of natural genetic variation on vascular matrix remodeling has begun to shed new light on the importance of these genes in atherogenesis.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 10865823 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
7: Matrix Biol. 1997 Mar;15(8-9):527-33.
Mighty mice: transgenic technology "knocks out" questions of matrix metalloproteinase function.
Shapiro SD.
Department of Medicine, Washington University School of Medicine, Barnes Jewish Hospital, St. Louis, Missouri, USA.
Matrix metalloproteinases (MMP) comprise a family of structurally related proteinases that are believed to play a critical role in many physiological and pathological processes. Transgenic technology offers the possibility of determining whether MMPs contribute directly to these processes. For example, gain of function and loss of function models have confirmed causative roles of MMPs in the development of pulmonary emphysema and unexpectedly uncovered an MMP-dependent mechanism of inflammatory cell recruitment. Limitations of these techniques and powerful applications on the horizon are also presented as we embark on an era where controlled experiments can be performed in complex mammalian models.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 9138285 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
8: Matrix Biol. 1997 Mar;15(8-9):511-8.
Relating matrix metalloproteinase structure to function: why the "hemopexin" domain?
Murphy G, Knäuper V.
Strangeways Research Laboratory, Cambridge, United Kingdom.
Matrix metalloproteinases are thought to be key players in the remodelling activity of cells associated with both physiological and pathological processes. They share a relatively conserved structure with a number of identifiable modules linked to their specific functions. The structure of the individual domains of a number of matrix metalloproteinases have now been elucidated. Here we review these data in the light of complementary studies on the behaviour of these enzymes in biological systems. In particular we focus on the C-terminal hemopexin-like domain which has intriguingly specific roles in individual matrix metalloproteinases.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 9138283 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
9: Enzyme Protein. 1996;49(1-3):38-58.
What structure and function of avian plasminogen activator and matrix metalloproteinase-2 reveal about their counterpart mammalian enzymes, their regulation and their role in tumor invasion.
Alexander DS, Aimes RT, Quigley JP.
Department of Cellular and Molecular Pathology, SUNY at Stony Brook 11794-8691, USA.
Rous sarcoma virus-transformed chick embryo fibroblasts (RSVCEF) constitute a well-characterized model system for oncogenic transformation, matrix degradation, and cancer invasion. As RSVCEF cultures employ both serine protease and metalloprotease cascades in the process of matrix degradation, they have contributed significantly to understanding the nature and regulation of these molecules involved in invasive cell behavior. RSVCEF produce elevated levels of a matrix metalloprotease-2 (MMP-2) whose hemopexin domain differs from mammalian MMP-2. The majority of MMP-2 produced by RSVCEF is present in a TIMP-free form which enhances its activation, catalytic activity and substrate specificity and therefore its matrix-degrading ability. RSVCEFs also exhibit high levels of urokinase-type plasminogen activator (uPA), which is found in active form in their conditioned medium in complete absence of plasminogen. Recombinantly expressed avian uPA is also in active form, while an active-site mutant of the same maintains its zymogen form, indicating the mechanism of activation of chicken uPA is autocatalytic. A domain and sequence comparison between chicken and human uPA attempts to identify motifs potentially responsible for the zymogen instability of avian uPA and its capability to autoactivate.
Publication Types:
Review
PMID: 8796996 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
10: Immun Infekt. 1993 Apr;21 Suppl 1:20-1.
[The matrix metalloproteinase gene family: structure, function, expression, and role in destructive joint disease]
[Article in German]
Conca W.
Abteilung Rheumatologie und Klinische Immunologie, Medizinische Universitätsklinik Freiburg.
The matrix metalloproteinases, i.e. collagenases, gelatinases and stromelysins, are members of a gene family. They are capable of degrading every component of the extracellular matrix. Tissue destruction observed in inflammatory joint disease is largely accounted for by the action of these enzymes. Among the most potent inducers of metalloproteinase expression are the inflammatory cytokines IL-1 and TNF-alpha. Studies of mechanisms of induction by these mediators at the transcriptional level have improved our understanding of the biological controls of metalloproteinase synthesis. Cytokine inhibitors might serve to inhibit or postpone the crippling consequences of metalloproteinase action.
Publication Types:
English Abstract
Review
PMID: 8344678 [PubMed - indexed for MEDLINE]
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