Viral infection and the evolution of caspase 8-regulated apoptotic and necrotic death pathways

Edward S. Mocarski, Jason W. Upton, William J. Kaiser

Research output: Contribution to journalReview articlepeer-review

183 Scopus citations

Abstract

Pathogens specifically target both the caspase 8-dependent apoptotic cell death pathway and the necrotic cell death pathway that is dependent on receptor-interacting protein 1 (RIP1; also known as RIPK1) and RIP3 (also known as RIPK3). The fundamental co-regulation of these two cell death pathways emerged when the midgestational death of mice deficient in FAS-associated death domain protein (FADD) or caspase 8 was reversed by elimination of RIP1 or RIP3, indicating a far more entwined relationship than previously appreciated. Thus, mammals require caspase 8 activity during embryogenesis to suppress the kinases RIP1 and RIP3 as part of the dialogue between two distinct cell death processes that together fulfil reinforcing roles in the host defence against intracellular pathogens such as herpesviruses.

Original languageEnglish (US)
Pages (from-to)79-88
Number of pages10
JournalNature Reviews Immunology
Volume12
Issue number2
DOIs
StatePublished - Feb 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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