J Biol Chem. 2005 May 20;280(20):19836-42.
Epub 2005 Mar 16. Caspase-10 triggers Bid
cleavage and caspase cascade activation in FasL-induced apoptosis. ·
Milhas
D, Cuvillier
O, Therville
N, Clave P, Thomsen M,
Levade
T, Benoist
H, Segui
B. INSERM U466, Institut Louis Bugnard, In contrast to caspase-8, controversy exists as to the
ability of caspase-10 to mediate apoptosis in response to FasL. Herein, we have shown activation of caspase-10,
-3, and -7 as well as B cell lymphoma-2-interacting domain (Bid) cleavage
and cytochrome c release in caspase-8-deficient Jurkat (I9-2) cells treated with FasL.
Apoptosis was clearly induced as illustrated by nuclear and DNA
fragmentation. These events were inhibited by benzyloxycarbonyl-VAD-fluoromethyl
ketone, a broad spectrum caspase
inhibitor, indicating that caspases were
functionally and actively involved. Benzyloxycarbonyl-AEVD-fluoromethyl
ketone, a caspase-10 inhibitor, had a comparable
effect. FasL-induced cell death was not
completely abolished by caspase inhibitors in
agreement with the existence of a cytotoxic caspase-independent pathway. In subpopulations of I9-2
cells displaying distinct caspase-10 expression levels, cell sensitivity to
FasL correlated with caspase-10 expression. A
robust caspase activation, Bid cleavage, and DNA
fragmentation were observed in cells with high caspase-10 levels but not in
those with low levels. In vitro, caspase-10, as well as caspase-8, could
cleave Bid to generate active truncated Bid (p15). Altogether, our data
strongly suggest that caspase-10 can serve as an initiator caspase in Fas signaling
leading to Bid processing, caspase cascade
activation, and apoptosis. PMID: 15772077 [PubMed -
indexed for MEDLINE]
