Fanconi anemia C protein acts at a switch between apoptosis and necrosis in mitomycin C-induced cell death

Citation
C. Guillouf et al., Fanconi anemia C protein acts at a switch between apoptosis and necrosis in mitomycin C-induced cell death, EXP CELL RE, 246(2), 1999, pp. 384-394
Citations number
73
Categorie Soggetti
Cell & Developmental Biology
Journal title
EXPERIMENTAL CELL RESEARCH
ISSN journal
00144827 → ACNP
Volume
246
Issue
2
Year of publication
1999
Pages
384 - 394
Database
ISI
SICI code
0014-4827(19990201)246:2<384:FACPAA>2.0.ZU;2-T
Abstract
Deregulation of apoptosis seems to be a hallmark of the Fanconi anemia (FA) syndrome. In order to further define the role of the FA protein from compl ementation group C (FAC) in apoptosis, we characterized parameters modified during the mitomycin-C (MMC)-induced apoptotic program. It is shown that d espite a higher level of cell death for FA compared to normal lymphoblasts after MMC treatment, FA cells do not display a marked DNA fragmentation. Fu rthermore, while playing a central role in MMC apoptosis of normal lymphobl asts, the activity of caspase-3-like proteases is altered in FA cells. Inte restingly, the disruption of the mitochondrial transmembrane potential (Del ta psi), an early event that can lead to apoptotic or to necrotic death, is accomplished similarly in FA and in normal cells. Finally, it is shown tha t the overexpressed FAC protein inhibited the apoptotic steps, with the exc eption of the decrease of the Delta psi Altogether, our results indicate th at the FAC protein acts at a step preceding the activation of the caspases and after the modification of the Delta psi, a decision point at which cell s can be pushed toward either apoptosis or necrosis and which, consequently , regulates the balance between the two modes of cell death. (C) 1999 Acade mic Press.