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The matrix protein CCN1 (CYR61) induces apoptosis in fibroblasts

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Title: The matrix protein CCN1 (CYR61) induces apoptosis in fibroblasts
Author(s): Todorovic, Viktor; Chen, Chih-Chiun; Hay, Nissim; Lau, Lester F.
Subject(s): human skin fibroblasts focal adhesion kinase mouse embryonic fibroblast umbilical vein endothelial cell Fibroblasts
Abstract: Integrin-mediated cell adhesion to extracellular matrix proteins is known to promote cell survival, whereas detachment from the matrix can cause rapid apoptotic death in some cell types. Contrary to this paradigm, we show that fibroblast adhesion to the angiogenic matrix protein CCN1 ( CYR61) induces apoptosis, whereas endothelial cell adhesion to CCN1 promotes cell survival. CCN1 induces fibroblast apoptosis through its adhesion receptors, integrin alpha(6)beta(1) and the heparan sulfate proteoglycan ( HSPG) syndecan-4, triggering the transcription-independent p53 activation of Bax to render cytochrome c release and activation of caspase-9 and -3. Neither caspase-8 activity nor de novo transcription or translation is required for this process. These results show that cellular interaction with a specific matrix protein can either induce or suppress apoptosis in a cell type-specific manner and that integrin alpha(6)beta(1)-HSPGs can function as receptors to induce p53-dependent apoptosis.
Issue Date: 2005-11-07
Publisher: Rockefeller University Press
Citation Info: Todorovic, V., C. C. Chen, N. Hay, and L. F. Lau, 2005, The matrix protein CCN1 (CYR61) induces apoptosis in fibroblasts: Journal of Cell Biology, v. 171, no. 3, p. 559-568
Type: Article
Description: Copyright:
ISSN: 0021-9525
Date Available in INDIGO: 2008-08-28

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