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Updated: Jun 12, 2026

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

c-FLIPL enhances anti-apoptotic Akt functions by modulation of Gsk3β activity

C Quintavalle1, M Incoronato, L Puca

  • 1Department of Cellular and Molecular Biology and Pathology, Federico II University of Naples, Naples, Italy.

Cell Death and Differentiation
|May 29, 2010
PubMed

Insights

This study identifies a new interaction between Akt and c-FLIP(L), revealing a novel mechanism for cancer cells to resist apoptosis. This discovery sheds light on unexpected functions of c-FLIP(L) in cell survival pathways.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Cancer Research

Background:

  • Akt is a key kinase regulating cell survival and apoptosis.
  • c-FLIP(L) inhibits apoptosis via the caspase-8 pathway.
  • Understanding Akt interactors is crucial for cancer therapy.

Purpose of the Study:

  • To identify novel Akt-interacting proteins.
  • To elucidate the functional consequences of the Akt-c-FLIP(L) interaction.
  • To explore new mechanisms of cancer cell resistance to apoptosis.

Main Methods:

  • Yeast two-hybrid screening using Akt as bait.
  • Co-immunoprecipitation to confirm protein interactions.
  • Analysis of protein phosphorylation, gene expression, and apoptosis assays.

Main Results:

  • Identified c-FLIP(L) as an Akt interactor.
  • Confirmed Akt and c-FLIP(L) interaction via co-immunoprecipitation.
  • Demonstrated that c-FLIP(L) overexpression confers resistance to TRAIL-induced apoptosis by affecting Gsk3β, p27(Kip1), and caspase-3.

Conclusions:

  • A novel Akt-c-FLIP(L) interaction pathway regulates apoptosis.
  • c-FLIP(L) plays an unexpected role in mediating resistance to TRAIL-induced apoptosis in cancer cells.
  • This interaction offers potential therapeutic targets for overcoming cancer resistance.

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