Redundant and receptor-specific activities of TRADD, RIPK1 and FADD in death receptor signaling.
Cell Death Dis
; 10(2): 122, 2019 02 11.
Article
em En
| MEDLINE
| ID: mdl-30741924
ABSTRACT
We evaluated redundant and receptor-specific activities of TRADD, RIPK1, and FADD in RIPK3-expressing HeLa cells lacking expression of these proteins or any combination of two of these factors. We confirmed the opposing role of FADD in TNF- and TRAIL-induced necroptosis and observed an anti-necroptotic function of TRADD. RIPK1 and TRADD act in a redundant manner in TNF- but not TRAIL-induced apoptosis. Complementary, FADD proved to be sufficient for TRAIL- but not for TNF-induced apoptosis. TRADD and RIPK1, however, redundantly mediated proinflammatory signaling in response to TNF and TRAIL. FADD deficiency sensitized more efficiently for TNFR1-mediated necroptosis than caspase-8 deficiency pointing to a caspase-8 independent inhibitory activity of FADD on TNF-induced necroptosis. Based on these characteristics, we propose a model in which the death receptor-specific activities of TRADD, RIPK1, and FADD are traced back to their hierarchically different position in TNFR1- and TRAIL death receptor signaling.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Proteína Serina-Treonina Quinases de Interação com Receptores
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Proteína de Domínio de Morte Associada a Fas
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Proteína de Domínio de Morte Associada a Receptor de TNF
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article