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Structural basis of cell apoptosis and necrosis in TNFR signaling

Jing Huang1, Shaoning Yu, Chaoneng Ji

  • 1State Key Laboratory of Genetic Engineering and School of Life Sciences, Fudan University, Shanghai, 200438, China.

Apoptosis : an International Journal on Programmed Cell Death
|December 3, 2014
PubMed

Insights

Tumor necrosis factor receptors (TNFRs) are crucial for immunity, regulating cell survival, apoptosis, and programmed necrosis. Recent structural studies of TNFR signaling complexes offer new insights into cell signaling mechanisms.

Area of Science:

  • Immunology
  • Molecular Biology
  • Structural Biology

Background:

  • Tumor necrosis factor receptors (TNFRs) are key mediators in both innate and adaptive immune responses.
  • TNFR signaling can initiate diverse cellular outcomes, including survival, apoptosis, and programmed necrosis, depending on cellular context.

Purpose of the Study:

  • To review recent advancements in the structural elucidation of the TNFR signaling pathway.
  • To explore the structural underpinnings of high-order signaling complexes involved in TNFR pathways.

Main Methods:

  • Review of recent structural biology studies focusing on TNFR signaling.
  • Analysis of the structural architecture of key signaling complexes like DISC, ripoptosome, and necrosome.

Main Results:

  • Detailed structural insights into high-order signal complexes such as the DISC, ripoptosome, and necrosome (including RIP3/MLKL complex).
  • Identification of the structural basis for the formation and function of these signaling platforms.

Conclusions:

  • The structural basis of TNFR-mediated signaling complexes provides critical information on cellular fate determination.
  • Understanding these structures may illuminate the biophysical principles governing complex cell signaling cascades.

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