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J. Cell Biol. 171 (3): 559-568

Copyright © 2005 by the Rockefeller University Press.


Article

The matrix protein CCN1 (CYR61) induces apoptosis in fibroblasts

Viktor Todorovicç, Chih-Chiun Chen, Nissim Hay, , and Lester F. Lau

Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago College of Medicine, Chicago, IL 60607

Correspondence to Lester F. Lau: LFLau{at}uic.edu

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}6ß1 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}6ß1-HSPGs can function as receptors to induce p53-dependent apoptosis.

Abbreviations used in this paper: DRB, 5,6-dichloro-1-ß-D-ribofuranosylbenzimidazole; FN, fibronectin; HSF, human skin fibroblast; HSPG, heparan sulfate proteoglycan; HUVEC, human umbilical vein endothelial cell; JNK, c-Jun NH2-terminal kinase; LN, laminin; MEF, mouse embryonic fibroblast; PLL, poly-L-lysine; VN, vitronectin.


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