Functional dichotomy of A20 in apoptotic and necrotic cell death

Peter Storz, Heike Döppler, Christiane Ferran, Shane T. Grey, Alex Toker

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


ROS (reactive oxygen species) play important roles in the progression of a number of human pathologies. ROS promote cell death, but can also induce gene transcription. The transcription factor NF-κB (nuclear factor κB) plays a critical role in oxidative stress responses. One of the proteins regulated by NF-κB is the zinc-finger protein A20. In TNF (tumour necrosis factor)-α signalling, NF-κB induction of A20 leads to increased cell survival. In the present paper, we show that in response to oxidative stress, A20 actually enhances cell death by necrosis, but not by apoptosis. Exposure of cells to ROS leads to the up-regulation of A20 which acts via a negative-feedback loop to block NF-κB activation and cellular survival. Silencing of A20 by RNAi (RNA interference) increases both the induction of NF-κB and the subsequent survival of cells exposed to high doses of oxidative stress, which, in untreated cells, promotes death by necrosis. Cells which express high basal levels of A20 are less protected from oxidative-stress-induced cell death when compared with cells with lower A20 expression. We also show that A20 regulates NF-κB by blocking the degradation of IκB (inhibitory protein κB) α. These data highlight a novel role for A20 in oxidative stress responses by terminating NF-κB-dependent survival signalling and thus sensitizing cells to death by necrosis.

Original languageEnglish (US)
Pages (from-to)47-55
Number of pages9
JournalBiochemical Journal
Issue number1
StatePublished - Apr 1 2005


  • A20
  • Apoptosis
  • Necrosis
  • Nuclear factor κB (NF-κB)
  • Oxidative stress
  • Reactive oxygen species (ROS)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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