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Updated: Nov 8, 2025

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
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Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

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Rictor, an essential component of mTOR complex 2, undergoes caspase-mediated cleavage during apoptosis induced by

Liqun Zhao1, Lei Zhu1,2, You-Take Oh1

  • 1Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, 1365-C Clifton Road NE, Atlanta, GA, 30322, USA.

Apoptosis : an International Journal on Programmed Cell Death
|April 27, 2021
PubMed

Insights

The protein rictor, a component of mTOR complex 2 (mTORC2), is cleaved by caspase-3 during apoptosis. This cleavage provides new insights into rictor

Area of Science:

  • Cellular biology
  • Molecular mechanisms of apoptosis
  • Protein regulation

Background:

  • Caspase-mediated protein cleavage is crucial for apoptosis.
  • Rapamycin-insensitive companion of mTOR (rictor) is a key component of mTOR complex 2 (mTORC2) regulating cellular homeostasis.
  • The role of rictor in apoptosis remains largely uncharacterized.

Purpose of the Study:

  • To investigate the role of rictor in apoptosis.
  • To determine if rictor is a substrate for caspases during apoptosis.

Main Methods:

  • Inducing apoptosis in cells using TRAIL and AZD9291.
  • Inhibiting caspases to assess rictor cleavage.
  • In vitro cleavage assays with purified rictor protein and caspase-3.
  • Mapping the caspase-3 cleavage site on rictor.

Main Results:

  • Rictor undergoes cleavage into ~50 kD and ~130 kD fragments during apoptosis induced by various stimuli.
  • Cleavage is caspase-dependent and can be replicated in vitro with caspase-3.
  • The specific caspase-3 cleavage site on rictor was identified as D1244 (VGVD).

Conclusions:

  • Rictor is a direct substrate of caspase-3 and is cleaved during the apoptotic process.
  • These findings expand the understanding of rictor's function in cell survival and growth regulation.
  • Rictor cleavage represents a novel event in the execution phase of apoptosis.
Keywords:
ApoptosisEGFR-TKIsRictorTRAIL

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