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Embryogenesis and Adult Life in the Absence of Intrinsic Apoptosis Effectors BAX, BAK, and BOK.
Ke, Francine F S; Vanyai, Hannah K; Cowan, Angus D; Delbridge, Alex R D; Whitehead, Lachlan; Grabow, Stephanie; Czabotar, Peter E; Voss, Anne K; Strasser, Andreas.
Afiliação
  • Ke FFS; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Victoria 3052, Australia. Electronic address: ke@wehi.edu.au.
  • Vanyai HK; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Victoria 3052, Australia.
  • Cowan AD; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Victoria 3052, Australia.
  • Delbridge ARD; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Victoria 3052, Australia.
  • Whitehead L; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
  • Grabow S; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Victoria 3052, Australia.
  • Czabotar PE; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Victoria 3052, Australia.
  • Voss AK; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Victoria 3052, Australia. Electronic address: avoss@wehi.edu.au.
  • Strasser A; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Victoria 3052, Australia. Electronic address: strasser@wehi.edu.au.
Cell ; 173(5): 1217-1230.e17, 2018 05 17.
Article em En | MEDLINE | ID: mdl-29775594
ABSTRACT
Intrinsic apoptosis, reliant on BAX and BAK, has been postulated to be fundamental for morphogenesis, but its precise contribution to this process has not been fully explored in mammals. Our structural analysis of BOK suggests close resemblance to BAX and BAK structures. Notably, Bok-/-Bax-/-Bak-/- animals exhibited more severe defects and died earlier than Bax-/-Bak-/- mice, implying that BOK has overlapping roles with BAX and BAK during developmental cell death. By analyzing Bok-/-Bax-/-Bak-/- triple-knockout mice whose cells are incapable of undergoing intrinsic apoptosis, we identified tissues that formed well without this process. We provide evidence that necroptosis, pyroptosis, or autophagy does not substantially substitute for the loss of apoptosis. Albeit very rare, unexpected attainment of adult Bok-/-Bax-/-Bak-/- mice suggests that morphogenesis can proceed entirely without apoptosis mediated by these proteins and possibly without cell death in general.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Apoptose / Proteínas Proto-Oncogênicas c-bcl-2 / Embrião de Mamíferos / Proteína X Associada a bcl-2 / Proteína Killer-Antagonista Homóloga a bcl-2 Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Apoptose / Proteínas Proto-Oncogênicas c-bcl-2 / Embrião de Mamíferos / Proteína X Associada a bcl-2 / Proteína Killer-Antagonista Homóloga a bcl-2 Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article