Individual caspase-10 isoforms play distinct and opposing roles in the initiation of death receptor-mediated tumour cell apoptosis.

Details

Ressource 1Download: Cell Death and Disease 2011.pdf (987.51 [Ko])
State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_FAD3E0711522
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Individual caspase-10 isoforms play distinct and opposing roles in the initiation of death receptor-mediated tumour cell apoptosis.
Journal
Cell death & disease
Author(s)
Mühlethaler-Mottet A, Flahaut M, Bourloud KB, Nardou K, Coulon A, Liberman J, Thome M, Gross N
Publication state
Published
Issued date
03/2011
Peer-reviewed
Oui
Language
english
Abstract
The cysteine protease caspase-8 is an essential executioner of the death receptor (DR) apoptotic pathway. The physiological function of its homologue caspase-10 remains poorly understood, and the ability of caspase-10 to substitute for caspase-8 in the DR apoptotic pathway is still controversial. Here, we analysed the particular contribution of caspase-10 isoforms to DR-mediated apoptosis in neuroblastoma (NB) cells characterised by their resistance to DR signalling. Silencing of caspase-8 in tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-sensitive NB cells resulted in complete resistance to TRAIL, which could be reverted by overexpression of caspase-10A or -10D. Overexpression experiments in various caspase-8-expressing tumour cells also demonstrated that caspase-10A and -10D isoforms strongly increased TRAIL and FasL sensitivity, whereas caspase-10B or -10G had no effect or were weakly anti-apoptotic. Further investigations revealed that the unique C-terminal end of caspase-10B was responsible for its degradation by the ubiquitin–proteasome pathway and for its lack of pro-apoptotic activity compared with caspase-10A and -10D. These data highlight in several tumour cell types, a differential pro- or anti-apoptotic role for the distinct caspase-10 isoforms in DR signalling, which may be relevant for fine tuning of apoptosis initiation.
Keywords
caspase-10, caspase-8, apoptosis, TRAIL, neuroblastoma
Pubmed
Open Access
Yes
Create date
23/03/2020 11:44
Last modification date
26/06/2020 6:11
Usage data