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Cathepsin S cannibalism of cathepsin K as a mechanism to reduce type I collagen degradation.


ABSTRACT: Cathepsins S and K are potent mammalian proteases secreted into the extracellular space and have been implicated in elastin and collagen degradation in diseases such as atherosclerosis and osteoporosis. Studies of individual cathepsins hydrolyzing elastin or collagen have provided insight into their binding and kinetics, but cooperative or synergistic activity between cathepsins K and S is less described. Using fluorogenic substrate assays, Western blotting, cathepsin zymography, and computational analyses, we uncovered cathepsin cannibalism, a novel mechanism by which cathepsins degrade each other as well as the substrate, with cathepsin S predominantly degrading cathepsin K. As a consequence of these proteolytic interactions, a reduction in total hydrolysis of elastin and type I collagen

SUBMITTER: Barry ZT 

PROVIDER: S-EPMC3431690 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature