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Caspases

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 Intrinsic Apoptotic Pathway

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...

The Extrinsic Apoptotic Pathway

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...

Apoptosis

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.

Anaphase Promoting Complex

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...

Phagocytosis of Apoptotic Cells

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.

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Related Experiment Video

Updated: Jun 22, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

The Apaf-1*procaspase-9 apoptosome complex functions as a proteolytic-based molecular timer.

Srinivas Malladi¹, Madhavi Challa-Malladi, Howard O Fearnhead

¹Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712-0125, USA.

The EMBO Journal

|June 5, 2009

Summary

The Apaf-1 apoptosome acts as a molecular timer for apoptosis. Procaspase-9 binding and autoprocessing activate this timer, with its dissociation rate dictating the speed of apoptosis.

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Area of Science:

Cell Biology
Biochemistry
Molecular Biology

Background:

Initiator caspase-9 activation by the Apaf-1 apoptosome is crucial for stress-induced apoptosis.
Activated caspase-9 must remain bound to the apoptosome for sustained catalytic activity.

Purpose of the Study:

To elucidate the mechanism of procaspase-9 processing by the Apaf-1 apoptosome.
To understand the role of caspase-9 dissociation from the apoptosome in regulating apoptosis.

Main Methods:

Investigated caspase-9 processing via a CARD-displacement mechanism.
Analyzed the binding affinity of procaspase-9 and processed caspase-9 to the apoptosome.
Characterized the kinetics of caspase-9 dissociation and its impact on procaspase-3 activation.

Main Results:

Apoptosome-mediated cleavage of procaspase-9 occurs through CARD displacement, not typical substrate processing.
Procaspase-9 exhibits higher affinity for the apoptosome, displacing processed caspase-9 and enabling a continuous activation cycle.
Rapid caspase-9 autoprocessing limits its direct contribution to procaspase-3 activation.

Conclusions:

The Apaf-1 apoptosome functions as a proteolytic molecular timer.
Procaspase-9 concentration and autoprocessing rate set the timer's duration.
The dissociation rate of processed caspase-9 from the apoptosome determines the timer's speed, regulating apoptosis progression.