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Related Concept Videos

Caspases01:24

Caspases

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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...
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The Extrinsic Apoptotic Pathway01:17

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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...
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The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

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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...
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Related Experiment Video

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Identifying Caspases and their Motifs that Cleave Proteins During Influenza A Virus Infection
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A caspase finds a target.

Amy E Baek1

  • 1Science Signaling, AAAS, Washington, DC 20005, USA.

Science Signaling
|December 12, 2023
PubMed
Summary

The noncanonical caspase-4 enzyme processes the precursor of IL-18 cytokine when stimulated by lipopolysaccharide (LPS). This reveals a key step in inflammatory pathway activation.

Area of Science:

  • Immunology
  • Cellular Biology
  • Biochemistry

Background:

  • Interleukin-18 (IL-18) is a crucial cytokine involved in inflammatory responses.
  • Caspase-4 is a noncanonical caspase implicated in innate immunity.
  • Processing of pro-IL-18 is essential for its activation and secretion.

Purpose of the Study:

  • To investigate the role of caspase-4 in the processing of pro-IL-18.
  • To elucidate the molecular mechanism by which lipopolysaccharide (LPS) triggers IL-18 maturation.

Main Methods:

  • Cell culture experiments using immune cells stimulated with LPS.
  • Western blot analysis to detect protein processing.
  • Enzyme activity assays for caspase-4.

Main Results:

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  • Caspase-4 was found to directly cleave pro-IL-18.
  • LPS stimulation led to the activation of caspase-4.
  • Inhibition of caspase-4 activity blocked IL-18 processing.

Conclusions:

  • Caspase-4 is the primary enzyme responsible for processing pro-IL-18 in response to LPS.
  • This finding highlights a critical pathway in LPS-induced inflammation.