Journal
BIOLOGICAL CHEMISTRY
Volume 390, Issue 2, Pages 91-97Publisher
WALTER DE GRUYTER GMBH
DOI: 10.1515/BC.2009.015
Keywords
homeostasis; knockout mice; matrix metalloproteinase; metastasis; protease web; systems biology
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Funding
- European Commission [FP6 LSHC-CT-2003-503297, FP7 HEALTH-2007-201279]
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Knockout mice are the gold standard to probe for the role of a specific protease within the interacting network of proteases, substrates, and inhibitors. This proteolytic network, or protease web, determines cell signaling and organ homeostasis. Therefore, protease deficiency or inhibition is intrinsically tied to alterations within this network, always leading to new molecular phenotypes, which define susceptibility of an organ to disease. Furthermore, recent hints, mainly from research on matrix metalloproteinases, about the impact of the protease web on inter-organ signaling molecules suggest the existence of a proteolytic internet of communicating local organ- or molecular polymorphism-specific networks, thereby defining homeostasis and disease susceptibility in the whole organism.
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