RIPK1 and RIPK3: critical regulators of inflammation and cell death

Trends Cell Biol. 2015 Jun;25(6):347-53. doi: 10.1016/j.tcb.2015.01.001. Epub 2015 Feb 4.

Abstract

RIPK1 and RIPK3 (receptor-interacting serine/threonine protein kinases 1/3) interact by virtue of their RIP homotypic interaction motifs to mediate a form of cell death called necroptosis, although mice lacking these kinases have very different phenotypes. RIPK1-deficient mice die soon after birth, whereas RIPK3-deficient mice are healthy. Necroptosis involves cell rupture and is triggered by tumor necrosis factor (TNF), Toll-like receptors (TLRs), or the T cell receptor (TCR) when pro-apoptotic caspase-8 is inhibited. Various mouse models of disease are ameliorated by RIPK3 deficiency, suggesting that necroptosis contributes to pathology. Genetic rescue experiments now reveal why RIPK3-deficient are viable but RIPK1-deficient mice are not. These and other experiments indicate unexpected complexity in the regulation of both apoptosis and necroptosis by RIPK1 and RIPK3.

Keywords: RIPK1; RIPK3; apoptosis; necroptosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Humans
  • Inflammation / metabolism*
  • Necrosis / metabolism*
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • RIPK1 protein, human
  • RIPK3 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases