Two mechanisms of caspase 9 processing in double-stranded RNA- and virus-triggered apoptosis.

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Serval ID
serval:BIB_426EB8A02047
Type
Article: article from journal or magazin.
Collection
Publications
Title
Two mechanisms of caspase 9 processing in double-stranded RNA- and virus-triggered apoptosis.
Journal
Apoptosis
Author(s)
Iordanov M.S., Ryabinina O.P., Schneider P., Magun B.E.
ISSN
1360-8185 (Print)
ISSN-L
1360-8185
Publication state
Published
Issued date
2005
Volume
10
Number
1
Pages
153-166
Language
english
Abstract
Viral double-stranded RNA (dsRNA) is a ubiquitous intracellular "alert signal" used by cells to detect viral infection and to mount anti-viral responses. DsRNA triggers a rapid (complete within 2-4 h) apoptosis in the highly-susceptible HeLa cell line. Here, we demonstrate that the apical event in this apoptotic cascade is the activation of procaspase 8. Downstream of caspase 8, the apoptotic signaling cascade bifurcates into a mitochondria-independent caspase 8/caspase 3 arm and a mitochondria-dependent, caspase 8/Bid/Bax/Bak/cytochrome c arm. Both arms impinge upon, and activate, procaspase 9 via two different cleavage sites within the procaspase 9 molecule (D330 and D315, respectively). This is the first in vivo demonstration that the "effector" caspase 3 plays an "initiator" role in the regulation of caspase 9. The dsRNA-induced apoptosis is potentiated by the inhibition of protein synthesis, whose role is to accelerate the execution of all apoptosis steps downstream of, and including, the activation of caspase 8. Thus, efficient apoptosis in response to viral dsRNA results from the co-operation of the two major apical caspases (8 and 9) and the dsRNA-activated protein kinase R (PKR)/ribonuclease L (RNase L) system that is essential for the inhibition of protein synthesis in response to viral infection.
Keywords
Apoptosis, Breast Neoplasms/pathology, Caspase 9, Caspases/metabolism, Cell Line, Tumor, Encephalomyocarditis virus/genetics, Encephalomyocarditis virus/physiology, Enzyme Activation, Female, Hela Cells, Humans, RNA, Double-Stranded/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
19/01/2008 18:30
Last modification date
20/08/2019 14:44
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