CASP8 activity is inhibited

Stable Identifier
R-HSA-5218900
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
CASP8 activity is inhibited
Click the image above or here to open this pathway in the Pathway Browser
Cell death triggered by extrinsic stimuli via death receptors or toll-like receptors (e.g., TLR3, TLR4) may result in either apoptosis or regulated necrosis (necroptosis) (Holler N et al. 2000; Kalai M et al. 2002; Kaiser WJ and Offermann MK 2005; Yang P et al. 2007). Caspase-8 (CASP8) is a cysteine protease, which functions as a key mediator for determining which form of cell death will occur (Kalai M et al. 2002). The proteolytic activity of a fully processed, heterotetrameric form of CASP8 in human and rodent cells is required for proapoptotic signaling and also for a cleavage of kinases RIPK1 and RIPK3, while at the same time preventing RIPK1/RIPK3-dependent regulated necrosis (Juo P et al. 1998; Lin Y et al. 1999; Holler N et al. 2000; Hopkins-Donaldson S et al. 2000). A blockage of CASP8 activity in the presence of caspase inhibitors such as Z-VAD-FMK (pan-caspase inhibitor), endogenous FLIP(S) or viral FLIP-like protein was found to switch signaling to necrotic cell death (Thome M et al. 1997; Kalai M et al. 2002; Feoktistova M et al. 2011; Sawai H 2013).
Literature References
PubMed ID Title Journal Year
12181749 Tipping the balance between necrosis and apoptosis in human and murine cells treated with interferon and dsRNA

Kalai, M, Van Loo, G, Vanden Berghe, T, Meeus, A, Burm, W, Saelens, X, Vandenabeele, P

Cell Death Differ. 2002
23410748 Differential effects of caspase inhibitors on TNF-induced necroptosis

Sawai, H

Biochem. Biophys. Res. Commun. 2013
9087414 Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors

Thome, M, Schneider, P, Hofmann, K, Fickenscher, H, Meinl, E, Neipel, F, Mattmann, C, Burns, K, Bodmer, JL, Schröter, M, Scaffidi, C, Krammer, PH, Peter, ME, Tschopp, J

Nature 1997
21737330 cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms

Feoktistova, M, Geserick, P, Kellert, B, Dimitrova, DP, Langlais, C, Hupe, M, Cain, K, MacFarlane, M, Häcker, G, Leverkus, M

Mol. Cell 2011
Participants
Events
Participates
as an event of
Event Information
Go Biological Process
negative regulation of endopeptidase activity (0010951)
Orthologous Events
CASP8 activity is inhibited (Bos taurus)
CASP8 activity is inhibited (Canis familiaris)
CASP8 activity is inhibited (Danio rerio)
CASP8 activity is inhibited (Drosophila melanogaster)
CASP8 activity is inhibited (Gallus gallus)
CASP8 activity is inhibited (Mus musculus)
CASP8 activity is inhibited (Rattus norvegicus)
CASP8 activity is inhibited (Sus scrofa)
Cross References
BioModels Database
Authored
Shamovsky, V  (2013-12-20)
Reviewed
Gillespie, ME  (2014-10-31)
Chan, FK  (2015-02-15)
Murphy, JM  (2020-08-28)
Created
Shamovsky, V  (2013-12-20)
Cite Us!