Activation of the NF-κB pathway by Caspase 8 and its homologs

Preet M. Chaudhary, Michael T. Eby, Alan Jasmin, Arvind Kumar, Li Liu, Leroy Hood

Research output: Contribution to journalArticle

181 Scopus citations

Abstract

Caspase 8 is the most proximal caspase in the caspase cascade and has been known for its role in the mediation of cell death by various death receptors belonging to the TNFR family. We have discovered that Caspase 8 can activate the NF-κB pathway independent of its activity as a pro-apoptotic protease. This property is localized to its N-terminal prodomain, which contains two homologous death effector domains (DEDs). Caspase 10 and MRIT, two DEDs-containing homologs of Caspase 8, can similarly activate the NF-κB pathway. Dominant-negative mutants of the Caspase 8 prodomain can block NF-κB induced by Caspase 8, FADD and several death receptors belonging to the TNFR family. Caspase 8 can interact with multiple proteins known to be involved in the activation of the NF-κB pathway, including the serine-threonine kinases RIP, NIK, IKK1 and IKK2. Thus, DEDs-containing caspases and caspase homolog(s) may have functions beyond their known role in the mediation of cell death.

Original languageEnglish (US)
Pages (from-to)4451-4460
Number of pages10
JournalOncogene
Volume19
Issue number39
DOIs
StatePublished - Sep 14 2000

Keywords

  • CFLIP
  • Caspase
  • Death effector domain
  • FADD
  • MRIT
  • NF-κB

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Chaudhary, P. M., Eby, M. T., Jasmin, A., Kumar, A., Liu, L., & Hood, L. (2000). Activation of the NF-κB pathway by Caspase 8 and its homologs. Oncogene, 19(39), 4451-4460. https://doi.org/10.1038/sj.onc.1203812