Related Experiment Video

Updated: Aug 21, 2026

Evaluation of Caspase Activation to Assess Innate Immune Cell Death
10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

Partial cleavage of RasGAP by caspases is required for cell survival in mild stress conditions

Jiang-Yan Yang1, David Michod, Joël Walicki

  • 1Department of Cellular Biology, Lausanne University, 1005 Lausanne, Switzerland.

Molecular and Cellular Biology
|November 16, 2004
PubMed

Insights

Cells activate survival pathways by partially cleaving Ras GTPase-activating protein (RasGAP) with caspase 3. This generates a fragment that activates antiapoptotic Akt kinase, preventing excessive apoptosis during stress.

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Apoptosis regulation is vital for multicellular organism development and homeostasis.
  • Cells employ antiapoptotic factors like Bcl2 family members to resist lethal stimuli.
  • Executioner caspases, central to apoptosis, require tight control to prevent cellular damage.

Purpose of the Study:

  • To elucidate a novel mechanism enabling cell survival following executioner caspase activation.
  • To investigate the role of Ras GTPase-activating protein (RasGAP) cleavage in cellular stress response.
  • To identify key molecular players in preventing excessive caspase activity.

Main Methods:

  • Utilized molecular biology techniques to study caspase-mediated protein cleavage.
  • Investigated the functional consequences of RasGAP partial cleavage in cellular models.
  • Employed mutant RasGAP to assess the necessity of cleavage for cell survival.

Main Results:

  • Identified partial cleavage of RasGAP by caspase 3 generates an antiapoptotic fragment (fragment N).
  • Demonstrated that fragment N activates Akt kinase, inhibiting further caspase amplification.
  • Showcased that cells with uncleavable RasGAP fail to activate Akt and undergo apoptosis under stress.

Conclusions:

  • Partial RasGAP cleavage by caspase 3 is a critical survival mechanism under stress.
  • This process involves a feedback loop where executioner caspases regulate their own activation.
  • The RasGAP-Akt pathway is essential for preventing excessive apoptosis and maintaining cellular homeostasis.

More Related Videos

Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis12:55

Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis

Published on: February 16, 2015

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

Related Concept Videos

Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...