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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

(Un)expected roles of c-IAPs in apoptotic and NFkappaB signaling pathways

Eugene Varfolomeev1, Domagoj Vucic

  • 1Department of Protein Engineering, Genentech, Inc. South San Francisco, California 94080, USA.

Cell Cycle (Georgetown, Tex.)
|May 13, 2008
PubMed

Insights

Inhibitor of apoptosis (IAP) proteins regulate cell death. Cellular IAP1 and 2 (c-IAP1/2) suppress TNFalpha-induced cell death and regulate NFkappaB signaling, offering therapeutic potential.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Inhibitor of apoptosis (IAP) proteins are key regulators of cell death pathways.
  • Cellular IAP1 and 2 (c-IAP1/2) have known anti-apoptotic functions but their precise physiological roles remain largely undefined.
  • Proposed mechanisms for IAP anti-apoptotic activity include direct inhibition and ubiquitination of pro-apoptotic factors, and activation of pro-survival signaling.

Purpose of the Study:

  • To elucidate the complex biological roles of c-IAP1 and c-IAP2.
  • To review recent advancements in understanding c-IAP1/2 functions.
  • To discuss the therapeutic implications of targeting c-IAPs.

Main Methods:

  • Review of recent scientific literature on c-IAP1/2.
  • Analysis of molecular mechanisms underlying c-IAP1/2 function.
  • Discussion of signaling pathways involving c-IAP1/2, including TNFalpha and NFkappaB pathways.

Main Results:

  • c-IAP1/2 suppress Tumor Necrosis Factor alpha (TNFalpha)-stimulated cell death by inhibiting the formation of the TNF Receptor 1 (TNFR1) pro-apoptotic signaling complex.
  • c-IAP1/2 regulate pro-survival NFkappaB signaling pathways, including ubiquitination of NFkappaB-inducing kinase (NIK) in the non-canonical pathway.
  • c-IAPs exhibit self-regulation of protein levels via RING domain-mediated auto-ubiquitination.

Conclusions:

  • c-IAP1/2 play multifaceted roles in both suppressing apoptosis and regulating pro-survival signaling.
  • Understanding these complex roles is crucial for developing targeted therapies.
  • Targeting c-IAPs presents a promising avenue for therapeutic intervention in various diseases.

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