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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...
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.
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...

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Related Experiment Video

Updated: Jun 16, 2026

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages
08:41

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages

Published on: April 6, 2022

Inflammatory stimuli regulate caspase substrate profiles.

Nicholas J Agard1, David Maltby, James A Wells

  • 1Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94158, USA.

Molecular & Cellular Proteomics : MCP
|February 23, 2010
PubMed
Summary
This summary is machine-generated.

Inflammatory caspases (caspase-1, -4, -5) have many substrates, but few were known. This study identified 82 new caspase-1 substrates, revealing inflammation

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Last Updated: Jun 16, 2026

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages
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Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages

Published on: April 6, 2022

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

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry
05:29

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry

Published on: March 24, 2023

Area of Science:

  • Immunology
  • Molecular Biology
  • Proteomics

Background:

  • Inflammatory caspases (caspase-1, -4, -5) regulate physiological processes in response to inflammatory signals.
  • Known substrates for these caspases are limited, primarily including other caspases and interleukin-1 family cytokines.
  • A comprehensive understanding of inflammatory caspase substrates is crucial for elucidating their roles in inflammation.

Purpose of the Study:

  • To comprehensively identify and characterize substrates cleaved by inflammatory caspases (caspase-1, -4, -5).
  • To compare substrate profiles induced by different inflammatory stimuli in vivo versus in vitro conditions.
  • To investigate the role of substrate localization in regulating inflammatory caspase activity.

Main Methods:

  • Utilized an enzymatic N-terminal enrichment method combined with mass spectrometry-based proteomics.
  • Analyzed THP-1 monocytic cell lysates treated with recombinant purified caspases (in vitro).
  • Investigated inflammatory caspases activated by gout mimics, bacterial infection, and viral infection mimics (in vivo), employing quantitative SILAC labeling.

Main Results:

  • Identified 82 putative caspase-1 substrates, 3 for caspase-4, and none for caspase-5 in vitro.
  • In vivo, activated inflammatory caspases cleaved 27 (gout mimic), 16 (bacterial mimic), and 22 (viral mimic) substrates.
  • In vivo stimuli induced overlapping but distinct substrate profiles, with only half of in vivo cleavages matching in vitro findings.

Conclusions:

  • This study provides the most extensive list of caspase-1-cleaved products to date, with caspases-4 and -5 having significantly fewer substrates.
  • Discrepancies between in vitro and in vivo data underscore the critical role of substrate localization in regulating inflammatory caspase activity.
  • Inflammation inducers may subtly modulate caspase-1 substrate profiles, impacting cellular responses.