Related Experiment Video

Updated: Aug 30, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

Caspase activation

Kelly M Boatright1, Guy S Salvesen

  • 1Program in Apoptosis and Cell Death, Burnham Institute, Department of Molecular Pathology, University of California, San Diego, La Jolla, CA 92037, USA.

Biochemical Society Symposium
|November 1, 2003
PubMed

Insights

Caspase activation, crucial for cell death, involves distinct mechanisms for initiator and executioner caspases. Recent research clarifies these differences, moving beyond simple proteolytic cleavage assumptions for initiator caspase activation.

Area of Science:

  • Molecular Biology
  • Cell Death Pathways
  • Biochemistry

Background:

  • Caspase activation is a critical, irreversible step in programmed cell death (apoptosis).
  • Inactive caspase zymogens must remain dormant until a death signal triggers their activation.
  • Proteolytic cleavage was the assumed activation mechanism for all caspases, including initiators.

Purpose of the Study:

  • To review the molecular mechanisms of caspase activation.
  • To emphasize recent findings challenging traditional caspase activation models.
  • To explain the differential activation requirements for initiator and executioner caspases.

Main Methods:

  • Literature review focusing on recent studies.
  • Analysis of molecular mechanisms governing caspase activation.
  • Comparative examination of initiator and executioner caspase activation pathways.

Main Results:

  • Recent studies on caspases-2, -8, and -9 challenge the universal proteolytic cleavage model for initiator caspase activation.
  • Distinct activation mechanisms exist for initiator and executioner caspases.
  • New research offers a coherent explanation for these differential requirements.

Conclusions:

  • Caspase activation is more complex than previously understood, with unique pathways for initiator caspases.
  • Understanding these distinct mechanisms is key to comprehending cell death regulation.
  • This review synthesizes current knowledge, highlighting the evolving paradigm of caspase activation.

More Related Videos

Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry05:29

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry

Published on: March 24, 2023

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 Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
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...