Title: Adenylyl cyclase-associated protein-1/CAP1 as a biological target substrate of gelatinase B/MMP-9
Authors: Cauwe, Bénédicte ×
Martens, Erik
Van den Steen, Philippe
Proost, Paul
Van Aelst, Ilse
Blockmans, Daniel Engelbert
Opdenakker, Ghislain #
Issue Date: Sep-2008
Publisher: Academic Press
Series Title: Experimental Cell Research vol:314 issue:15 pages:2739-2749
Abstract: Matrix rnetalloproteinases (MMPs) are classically associated with the turnover of secreted structural and functional proteins. Although MMPs have been shown to process also a kaleidoscope of membrane-associated Substrates, little is known about the processing of intracellular Proteins by MMPs. Physiological and pathological cell apoptosis, necrosis and tumor lysis by chemotherapy, radiotherapy or immunological cytotoxicity, are examples of conditions in which ail overload of intracellular proteins becomes accessible to the action of MMPs. We used a model system of dying human myelomonocytic cells to study the processing of intracellular protein substrates by gelatinase B/MMP-9 in vitro. Adenylyl cyclase-associated protein-1 or CAP1 was identified as a novel and most efficient substrate of gelatinase B/MMP-9. The presence of CAP1 in the extracellular milieu in vivo was documented by analysis Of Urine of patients with systemic autoimmune diseases. Whereas no active MMP-9 could be detected in urines of healthy controls, all urine samples of patients with clinical parameters of renal failure contained activated MMP-9 and/or MMP-2. In addition, in some of these patients indications of CAP1 cleavage are observed, implying CAP1 degradation in vivo. The high turnover rate of CAP1 by MMP-9, comparable to that of gelatin as the natural extracellular substrate of this enzyme, may be critical to prevent pathological conditions associated with considerable cytolysis. (c) 2008 Elsevier Inc. All rights reserved.
ISSN: 0014-4827
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Immunobiology (Rega Institute)
Laboratory of Molecular Immunology (Rega Institute)
Laboratory for Clinical Infectious and Inflammatory Disorders
Laboratory of Genetics of Autoimmunity (VIB-KU Leuven Center for Brain & Disease Research)
× corresponding author
# (joint) last author

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