Exposure of vital cells to necrotic cell lysates induce the IRE1α branch of the unfolded protein response and cell proliferation

Cell Stress Chaperones. 2018 Jan;23(1):77-88. doi: 10.1007/s12192-017-0825-6. Epub 2017 Jul 7.

Abstract

Necrosis is a form of cell death that is detrimental to the affected tissue because the cell ruptures and releases its content (reactive oxygen species among others) into the extracellular space. Clusterin (CLU), a cytoprotective extracellular chaperone has been shown to be upregulated in the face of necrosis. We here show that in addition to CLU upregulation, necrotic cell lysates induce JNK/SAPK signaling, the IRE1α branch of the unfolded protein response (UPR), the MAPK/ERK1/2, and the mTOR signaling pathways and results in an enhanced proliferation of the vital surrounding cells. We name this novel response mechanism: Necrosis-induced Proliferation (NiP).

Keywords: Clusterin; ERK; IRE1a; Necrosis; UPR; mTOR.

MeSH terms

  • Cell Proliferation
  • Cell Survival
  • Clusterin / metabolism
  • Endoribonucleases / metabolism*
  • HEK293 Cells
  • Heat-Shock Response
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Necrosis
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism*
  • Signal Transduction
  • Transcription Factor AP-1 / metabolism
  • Unfolded Protein Response*
  • X-Box Binding Protein 1 / metabolism

Substances

  • CLU protein, human
  • Clusterin
  • NF-kappa B
  • Transcription Factor AP-1
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • ERN1 protein, human
  • Protein Serine-Threonine Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Endoribonucleases