Cargando…
cIAPs Block Ripoptosome Formation, a RIP1/Caspase-8 Containing Intracellular Cell Death Complex Differentially Regulated by cFLIP Isoforms
The intracellular regulation of cell death pathways by cIAPs has been enigmatic. Here we show that loss of cIAPs promotes the spontaneous formation of an intracellular platform that activates either apoptosis or necroptosis. This 2 MDa intracellular complex that we designate “Ripoptosome” is necessa...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163271/ https://www.ncbi.nlm.nih.gov/pubmed/21737330 http://dx.doi.org/10.1016/j.molcel.2011.06.011 |
_version_ | 1782210936078073856 |
---|---|
author | Feoktistova, Maria Geserick, Peter Kellert, Beate Dimitrova, Diana Panayotova Langlais, Claudia Hupe, Mike Cain, Kelvin MacFarlane, Marion Häcker, Georg Leverkus, Martin |
author_facet | Feoktistova, Maria Geserick, Peter Kellert, Beate Dimitrova, Diana Panayotova Langlais, Claudia Hupe, Mike Cain, Kelvin MacFarlane, Marion Häcker, Georg Leverkus, Martin |
author_sort | Feoktistova, Maria |
collection | PubMed |
description | The intracellular regulation of cell death pathways by cIAPs has been enigmatic. Here we show that loss of cIAPs promotes the spontaneous formation of an intracellular platform that activates either apoptosis or necroptosis. This 2 MDa intracellular complex that we designate “Ripoptosome” is necessary but not sufficient for cell death. It contains RIP1, FADD, caspase-8, caspase-10, and caspase inhibitor cFLIP isoforms. cFLIP(L) prevents Ripoptosome formation, whereas, intriguingly, cFLIP(S) promotes Ripoptosome assembly. When cIAPs are absent, caspase activity is the “rheostat” that is controlled by cFLIP isoforms in the Ripoptosome and decides if cell death occurs by RIP3-dependent necroptosis or caspase-dependent apoptosis. RIP1 is the core component of the complex. As exemplified by our studies for TLR3 activation, our data argue that the Ripoptosome critically influences the outcome of membrane-bound receptor triggering. The differential quality of cell death mediated by the Ripoptosome may cause important pathophysiological consequences during inflammatory responses. |
format | Online Article Text |
id | pubmed-3163271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-31632712011-09-29 cIAPs Block Ripoptosome Formation, a RIP1/Caspase-8 Containing Intracellular Cell Death Complex Differentially Regulated by cFLIP Isoforms Feoktistova, Maria Geserick, Peter Kellert, Beate Dimitrova, Diana Panayotova Langlais, Claudia Hupe, Mike Cain, Kelvin MacFarlane, Marion Häcker, Georg Leverkus, Martin Mol Cell Article The intracellular regulation of cell death pathways by cIAPs has been enigmatic. Here we show that loss of cIAPs promotes the spontaneous formation of an intracellular platform that activates either apoptosis or necroptosis. This 2 MDa intracellular complex that we designate “Ripoptosome” is necessary but not sufficient for cell death. It contains RIP1, FADD, caspase-8, caspase-10, and caspase inhibitor cFLIP isoforms. cFLIP(L) prevents Ripoptosome formation, whereas, intriguingly, cFLIP(S) promotes Ripoptosome assembly. When cIAPs are absent, caspase activity is the “rheostat” that is controlled by cFLIP isoforms in the Ripoptosome and decides if cell death occurs by RIP3-dependent necroptosis or caspase-dependent apoptosis. RIP1 is the core component of the complex. As exemplified by our studies for TLR3 activation, our data argue that the Ripoptosome critically influences the outcome of membrane-bound receptor triggering. The differential quality of cell death mediated by the Ripoptosome may cause important pathophysiological consequences during inflammatory responses. Cell Press 2011-08-05 /pmc/articles/PMC3163271/ /pubmed/21737330 http://dx.doi.org/10.1016/j.molcel.2011.06.011 Text en © 2011 ELL & Excerpta Medica. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license |
spellingShingle | Article Feoktistova, Maria Geserick, Peter Kellert, Beate Dimitrova, Diana Panayotova Langlais, Claudia Hupe, Mike Cain, Kelvin MacFarlane, Marion Häcker, Georg Leverkus, Martin cIAPs Block Ripoptosome Formation, a RIP1/Caspase-8 Containing Intracellular Cell Death Complex Differentially Regulated by cFLIP Isoforms |
title | cIAPs Block Ripoptosome Formation, a RIP1/Caspase-8 Containing Intracellular Cell Death Complex Differentially Regulated by cFLIP Isoforms |
title_full | cIAPs Block Ripoptosome Formation, a RIP1/Caspase-8 Containing Intracellular Cell Death Complex Differentially Regulated by cFLIP Isoforms |
title_fullStr | cIAPs Block Ripoptosome Formation, a RIP1/Caspase-8 Containing Intracellular Cell Death Complex Differentially Regulated by cFLIP Isoforms |
title_full_unstemmed | cIAPs Block Ripoptosome Formation, a RIP1/Caspase-8 Containing Intracellular Cell Death Complex Differentially Regulated by cFLIP Isoforms |
title_short | cIAPs Block Ripoptosome Formation, a RIP1/Caspase-8 Containing Intracellular Cell Death Complex Differentially Regulated by cFLIP Isoforms |
title_sort | ciaps block ripoptosome formation, a rip1/caspase-8 containing intracellular cell death complex differentially regulated by cflip isoforms |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163271/ https://www.ncbi.nlm.nih.gov/pubmed/21737330 http://dx.doi.org/10.1016/j.molcel.2011.06.011 |
work_keys_str_mv | AT feoktistovamaria ciapsblockripoptosomeformationarip1caspase8containingintracellularcelldeathcomplexdifferentiallyregulatedbycflipisoforms AT geserickpeter ciapsblockripoptosomeformationarip1caspase8containingintracellularcelldeathcomplexdifferentiallyregulatedbycflipisoforms AT kellertbeate ciapsblockripoptosomeformationarip1caspase8containingintracellularcelldeathcomplexdifferentiallyregulatedbycflipisoforms AT dimitrovadianapanayotova ciapsblockripoptosomeformationarip1caspase8containingintracellularcelldeathcomplexdifferentiallyregulatedbycflipisoforms AT langlaisclaudia ciapsblockripoptosomeformationarip1caspase8containingintracellularcelldeathcomplexdifferentiallyregulatedbycflipisoforms AT hupemike ciapsblockripoptosomeformationarip1caspase8containingintracellularcelldeathcomplexdifferentiallyregulatedbycflipisoforms AT cainkelvin ciapsblockripoptosomeformationarip1caspase8containingintracellularcelldeathcomplexdifferentiallyregulatedbycflipisoforms AT macfarlanemarion ciapsblockripoptosomeformationarip1caspase8containingintracellularcelldeathcomplexdifferentiallyregulatedbycflipisoforms AT hackergeorg ciapsblockripoptosomeformationarip1caspase8containingintracellularcelldeathcomplexdifferentiallyregulatedbycflipisoforms AT leverkusmartin ciapsblockripoptosomeformationarip1caspase8containingintracellularcelldeathcomplexdifferentiallyregulatedbycflipisoforms |