Programmed necrosis and necroptosis signalling

FEBS J. 2015 Jan;282(1):19-31. doi: 10.1111/febs.13120. Epub 2014 Nov 11.

Abstract

In recent years, the paradigm of cell death regulation has changed. Nowadays, not only apoptosis but also several forms of necrosis (e.g. necroptosis) are considered to be regulated. The central roles of receptor-interacting serine/threonine protein kinase1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like protein, and the molecular signalling platforms in which these molecules participate, are being intensively studied. In particular, the role of RIPK1, being both a kinase and a scaffold molecule, in different cell death regulatory complexes is of great relevance for the field. This minireview aims to introduce the emerging and dynamic field of necroptosis to the reader, with a specific focus on intracellular signalling pathways involved in this process.

Keywords: cellular FLICE-inhibitory protein (cFLIP) isoforms; necroptosis; receptor-interacting serine/threonine protein kinase 1; receptor-interacting serine/threonine protein kinase 3; ripoptosome.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Humans
  • Mice
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Permeability Transition Pore
  • Models, Biological
  • Multiprotein Complexes / metabolism
  • Necrosis / metabolism*
  • Protein Kinases / metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*
  • Receptors, Death Domain / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Signal Transduction
  • Toll-Like Receptors / metabolism

Substances

  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Multiprotein Complexes
  • Receptors, Death Domain
  • Receptors, Tumor Necrosis Factor
  • Toll-Like Receptors
  • Protein Kinases
  • Receptor-Interacting Protein Serine-Threonine Kinases