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
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.