Related Experiment Video

Updated: Aug 6, 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

Proteolytic activation of executioner caspase-3 and -7 regulates different physiological processes in mice

Noëlle Sieg1,2, Johanna Stachelscheid1, Besarta Thaqi1

  • 1University of Cologne, Faculty of Medicine and University Hospital of Cologne, Institute for Molecular Immunology, Cologne, Germany.

The EMBO Journal
|July 21, 2026
PubMed

Insights

Caspase-3 (CASP3) and caspase-7 (CASP7) have distinct roles beyond apoptosis. While essential for embryonic development, their activation in adults is crucial for male fertility and lymphoid tissue development, respectively.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Developmental Biology

Background:

  • Caspase-3 (CASP3) and caspase-7 (CASP7) are executioner caspases.
  • They are activated by initiator caspases and were thought to have redundant roles due to similar activity.

Purpose of the Study:

  • To investigate the in vivo roles of CASP3 and CASP7 activation.
  • To determine if CASP3 and CASP7 have distinct functions in adult mice.
  • To explore non-apoptotic roles of caspases.

Main Methods:

  • Generation of knock-in mice expressing cleavage-resistant CASP3(D175A) or CASP7(D198A).
  • Analysis of embryonic development and adult tissue function in these mice.

Main Results:

  • Proteolytic activation is crucial for CASP3 and CASP7 activity in vivo.
  • Combined resistance to activation in both caspases leads to embryonic lethality, indicating redundant roles during development.
  • In adult mice, CASP7 activation is vital for male fertility (spermatogenesis).
  • CASP3 activation is critical for lymphoid tissue development via interferon signaling.
  • These distinct roles occur independently of apoptosis.

Conclusions:

  • CASP3 and CASP7 activation are essential for distinct physiological processes in adult mice.
  • Caspase activation plays significant roles in non-apoptotic functions.
  • Findings challenge the view of functional redundancy and suggest broader involvement in health and disease.

More Related Videos

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

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila13:21

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila

Published on: November 27, 2016

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 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...
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...
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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.