Checkpoints in TNF-Induced Cell Death: Implications in Inflammation and Cancer

Trends Mol Med. 2018 Jan;24(1):49-65. doi: 10.1016/j.molmed.2017.11.002. Epub 2017 Dec 5.

Abstract

Tumor necrosis factor (TNF) is a proinflammatory cytokine that coordinates tissue homeostasis by regulating cytokine production, cell survival, and cell death. However, how life and death decisions are made in response to TNF is poorly understood. Many inflammatory pathologies are now recognized to be driven by aberrant TNF-induced cell death, which, in most circumstances, depends on the kinase Receptor-interacting serine/threonine-protein kinase 1 (RIPK1). Recent advances have identified ubiquitin (Ub)-mediated phosphorylation of RIPK1 as belonging to crucial checkpoints for cell fate in inflammation and infection. A better understanding of these checkpoints might lead to new approaches for the treatment of chronic inflammatory diseases fueled by aberrant RIPK1-induced cell death, and/or reveal novel strategies for anticancer immunotherapies, harnessing the ability of RIPK1 to trigger immunogenic cell death.

Keywords: RIPK1; TNF; apoptosis; cell death; inflammation; necroptosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Death*
  • Humans
  • Inflammation / immunology*
  • Inflammation / pathology
  • NF-kappa B / immunology
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Receptor-Interacting Protein Serine-Threonine Kinases / immunology
  • Tumor Necrosis Factor-alpha / immunology*
  • Ubiquitin / immunology

Substances

  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Ubiquitin
  • RIPK1 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases