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Tumor necrosis factor-mediated cell death: to break or to burst, that's the question

Franky Van Herreweghe1, Nele Festjens, Wim Declercq

  • 1Unit For Molecular Signalling and Cell Death, Department for Molecular Biomedical Research, VIB, Technologiepark 927, 9052, Ghent (Zwijnaarde), Belgium.

Cellular and Molecular Life Sciences : CMLS
|March 4, 2010
PubMed

Insights

Tumor necrosis factor (TNF) triggers cell survival via NF-kappaB, apoptosis, or necroptosis. Caspases are key in apoptosis, while RIP1 and RIP3 kinases mediate necroptosis, revealing complex cell fate regulation.

Area of Science:

  • Cellular Biology
  • Immunology
  • Molecular Biology

Background:

  • Tumor necrosis factor (TNF) is a key mediator of cellular responses, including survival, apoptosis, and necrosis.
  • The precise molecular mechanisms governing the switch between these outcomes remain incompletely understood.

Purpose of the Study:

  • To review the signal-transduction pathways of major cellular responses induced by TNF.
  • To elucidate the roles of caspases, RIP1, and RIP3 in TNF-mediated cell death pathways.

Main Methods:

  • Review of existing literature on TNF signaling.
  • Analysis of experimental data on caspase inhibition and its effect on cell death.
  • Discussion of the role of receptor-interacting protein kinases (RIPK) in necroptosis.

Main Results:

  • TNF signaling can lead to cell survival through NF-kappaB activation.
  • Caspase recruitment and activation are critical for TNF-induced apoptosis.
  • Inhibition of caspases reveals an alternative necroptotic pathway dependent on RIP1 and RIP3 kinase activity.

Conclusions:

  • TNF signaling orchestrates diverse cellular outcomes, including survival and distinct forms of cell death (apoptosis and necroptosis).
  • Caspases actively suppress necroptosis, highlighting a complex regulatory network.
  • Understanding the molecular switches between cell survival and death is crucial for comprehending TNF's role in human diseases.

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