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Post-translational modifications as key regulators of TNF-induced necroptosis

X Liu1,2,3, F Shi1,2,3, Y Li1,2,3

  • 1Cancer Research Institute, Xiangya School of Medicine, Central South University, Hunan, China.

Cell Death & Disease
|July 8, 2016
PubMed

Insights

Necroptosis, a programmed cell death pathway, is regulated by post-translational modifications of key proteins like RIP1 and RIP3. These modifications control cell fate, determining survival or death via apoptosis or necroptosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Necroptosis is a distinct form of programmed cell death, independent of caspase activity.
  • Tumor necrosis factor (TNF)-induced necroptosis is a well-studied model.
  • Receptor-interacting protein kinases 1 and 3 (RIP1 and RIP3) are crucial for initiating necroptosis.

Purpose of the Study:

  • To review recent advances in understanding post-translational modifications in TNF-induced necroptosis.
  • To discuss how these modifications regulate programmed necrosis.
  • To elucidate the intricate control mechanisms governing cell death decisions.

Main Methods:

  • Review of existing literature on TNF-induced necroptosis.
  • Analysis of studies focusing on post-translational modifications of RIP1 and RIP3.
  • Integration of findings on ubiquitination, phosphorylation, caspase-mediated cleavage, and GlcNAcylation.

Main Results:

  • Post-translational modifications, including ubiquitination, phosphorylation, caspase 8-mediated cleavage, and GlcNAcylation, tightly control RIP1 and RIP3 activity.
  • These modifications are critical determinants of cell fate, dictating whether a cell undergoes apoptosis or necroptosis.
  • Coordinated regulation by these modifications fine-tunes the balance between cell survival and programmed cell death.

Conclusions:

  • Post-translational modifications play a pivotal role in regulating TNF-induced necroptosis.
  • Understanding these modifications is key to deciphering the complex control of programmed necrosis.
  • Further research into these regulatory events can offer insights into cell death pathways and potential therapeutic targets.

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