Cyclophilin A as negative regulator of apoptosis by sequestering cytochrome c.Report as inadecuate

Cyclophilin A as negative regulator of apoptosis by sequestering cytochrome c. - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 IRCM - Institut de recherche en cancérologie de Montpellier 2 CPBS - Centre d-études d-agents Pathogènes et Biotechnologies pour la Santé

Abstract : The release of cytochrome c from the mitochondrial intermembrane space is a decisive event in programmed cell death. Once in the cytoplasm, cytochrome c is involved in the formation of the macromolecular complex termed apoptosome, which activates procaspase-9 which in turn activates downstream procaspase-3. There are increasing evidence indicating that cyclophilin A is highly expressed in many tumors and cell lines where it exerts an anti-apoptotic function. In brain tissue, which over-expresses constitutively cyclophilin A, we found mixed dimers composed of cyclophilin A and cytochrome c. In a cell-free system we observed that pure cyclophilin A inhibited cytochrome c-dependent procaspase-3 activation. Moreover, we detected cyclophilin A-cytochrome c complexes within the cytoplasm of HCT116 cells following staurosporine-induced apoptosis. Our results strongly support that, in tumor cells, cyclophilin A is able to inhibit procaspase-3 activation by sequestering cytochrome c.

Keywords : phosphatidylethanolamine-binding protein Apoptosis brain tumour cyclophilin A cytochrome c procaspase-3 phosphatidylethanolamine-binding protein.

Author: Claude Bonfils - Nicole Bec - Christian Larroque - Maguy Del Rio - Céline Gongora - Martine Pugnière - Pierre Martineau -



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