Necroptosis is preceded by nuclear translocation of the signaling proteins that induce it

Cell Death Differ. 2016 Feb;23(2):253-60. doi: 10.1038/cdd.2015.92. Epub 2015 Jul 17.


A signaling pathway that induces programmed necrotic cell death (necroptosis) was reported to be activated in cells by several cytokines and various pathogen components. The major proteins participating in that pathway are the protein kinases RIPK1 and RIPK3 and the pseudokinase mixed lineage kinase domain-like protein (MLKL). Recent studies have suggested that MLKL, once activated, mediates necroptosis by binding to cellular membranes, thereby triggering ion fluxes. However, our knowledge of both the sequence of molecular events leading to MLKL activation and the subcellular sites of these events is fragmentary. Here we report that the association of MLKL with the cell membrane in necroptotic death is preceded by the translocation of phosphorylated MLKL, along with RIPK1 and RIPK3, to the nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • Apoptosis*
  • Cell Nucleus / metabolism*
  • HT29 Cells
  • HeLa Cells
  • Humans
  • Mice
  • Necrosis
  • Phosphorylation
  • Protein Kinases / metabolism
  • Protein Processing, Post-Translational
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction


  • Apoptosis Regulatory Proteins
  • MLKL protein, human
  • Protein Kinases
  • RIPK1 protein, human
  • RIPK3 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases