Linked Life Data

20812779

Source:http://linkedlifedata.com/resource/pubmed/id/20812779

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-9-15
pubmed:abstractText
Matrix metalloproteinases (MMPs), originally discovered to function in the breakdown of extracellular matrix proteins, have gained the status of regulatory proteases in signaling events by liganding and processing hormones, cytokines, chemokines, adhesion molecules and other membrane receptors. However, MMPs also cleave intracellular substrates and have been demonstrated within cells in nuclear, mitochondrial, various vesicular and cytoplasmic compartments, including the cytoskeletal intracellular matrix. Unbiased high-throughput degradomics approaches have demonstrated that many intracellular proteins are cleaved by MMPs, including apoptotic regulators, signal transducers, molecular chaperones, cytoskeletal proteins, systemic autoantigens, enzymes in carbohydrate metabolism and protein biosynthesis, transcriptional and translational regulators, and proteins in charge of protein clearance such as lysosomal and ubiquitination enzymes. Besides proteolysis inside cells, intracellular proteins may also be modulated by MMPs in the extracellular milieu. Indeed, many intracellular proteins exit cells by non-classical secretion mechanisms or by various conditions of cell death by apoptosis, necrosis and NETosis, and become accessible to extracellular proteases. Intracellular substrate proteolysis by MMPs is involved in innate immune defense and apoptosis, and affects oncogenesis and pathology of cardiac, neurological, protein conformational and autoimmune diseases, including ischemia-reperfusion injury, cardiomyopathy, Parkinson's disease, cataract, multiple sclerosis and systemic lupus erythematosus. Since the same MMP may affect physiology and pathology in different and even opposite ways, depending on its extracellular or subcellular localization, an additional layer of complexity is added to therapeutic MMP inhibition. Hence, further elucidation of intracellular MMP localizations and intracellular substrate proteolysis is a new challenge in MMP research.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1549-7798
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
351-423
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Intracellular substrate cleavage: a novel dimension in the biochemistry, biology and pathology of matrix metalloproteinases.
pubmed:affiliation
Rega Institute for Medical Research, Laboratory of Immunobiology, University of Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't