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RIPK1- and RIPK3-induced cell death mode is determined by target availability.
Cook, W D; Moujalled, D M; Ralph, T J; Lock, P; Young, S N; Murphy, J M; Vaux, D L.
Afiliación
  • Cook WD; La Trobe Institute for Molecular Science, La Trobe University, Kingsbury Drive, Bundoora, Victoria 3086, Australia.
  • Moujalled DM; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
  • Ralph TJ; La Trobe Institute for Molecular Science, La Trobe University, Kingsbury Drive, Bundoora, Victoria 3086, Australia.
  • Lock P; La Trobe Institute for Molecular Science, La Trobe University, Kingsbury Drive, Bundoora, Victoria 3086, Australia.
  • Young SN; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
  • Murphy JM; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
  • Vaux DL; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
Cell Death Differ ; 21(10): 1600-12, 2014 Oct.
Article en En | MEDLINE | ID: mdl-24902899
Both receptor-interacting protein kinase 1 (RIPK1) and RIPK3 can signal cell death following death receptor ligation. To study the requirements for RIPK-triggered cell death in the absence of death receptor signaling, we engineered inducible versions of RIPK1 and RIPK3 that can be activated by dimerization with the antibiotic coumermycin. In the absence of TNF or other death ligands, expression and dimerization of RIPK1 was sufficient to cause cell death by caspase- or RIPK3-dependent mechanisms. Dimerized RIPK3 induced cell death by an MLKL-dependent mechanism but, surprisingly, also induced death mediated by FADD, caspase 8 and RIPK1. Catalytically active RIPK3 kinase domains were essential for MLKL-dependent but not for caspase 8-dependent death. When RIPK1 or RIPK3 proteins were dimerized, the mode of cell death was determined by the availability of downstream molecules such as FADD, caspase 8 and MLKL. These observations imply that rather than a 'switch' operating between the two modes of cell death, the final mechanism depends on levels of the respective signaling and effector proteins.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Recombinantes / Apoptosis / Proteína Serina-Treonina Quinasas de Interacción con Receptores / Multimerización de Proteína Límite: Animals Idioma: En Revista: Cell Death Differ Año: 2014 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Recombinantes / Apoptosis / Proteína Serina-Treonina Quinasas de Interacción con Receptores / Multimerización de Proteína Límite: Animals Idioma: En Revista: Cell Death Differ Año: 2014 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido