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Related Concept Videos

The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

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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

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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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Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
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Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

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Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
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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 JAK-STAT Signaling Pathway

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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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Related Experiment Video

Updated: Feb 24, 2026

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
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AIM2 inflammasome activation and regulation: A structural perspective.

Bing Wang1, Qian Yin1

  • 1Department of Biological Science and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, United States.

Journal of Structural Biology
|August 17, 2017
PubMed
Summary
This summary is machine-generated.

The Absent in melanoma 2 (AIM2) inflammasome forms high-order helical filaments, not simple complexes, during activation. Structural studies reveal how these assemblies regulate dsDNA sensing, cytokine release, and pyroptosis.

Keywords:
AIM2ASCCARDCaspase-1Helical filamentHigh-order assemblyINCAInflammasomeP202PYDPolymerization

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Area of Science:

  • Immunology
  • Molecular Biology
  • Structural Biology

Background:

  • The Absent in melanoma 2 (AIM2) inflammasome is a key sensor of cytoplasmic dsDNA.
  • It comprises AIM2, ASC, and caspase-1, initiating inflammatory responses.
  • Dysregulation is linked to various diseases.

Purpose of the Study:

  • To review the step-by-step activation process of the AIM2 inflammasome.
  • To illustrate AIM2 inflammasome architecture and regulation using high-resolution structural data.
  • To highlight the role of high-order structure assembly in inflammasome function.

Main Methods:

  • Analysis of recent X-ray crystallography data.
  • Interpretation of high-resolution cryo-electron microscopy (cryo-EM) studies.
  • Review of structural mechanisms underlying AIM2 inflammasome assembly.

Main Results:

  • AIM2 inflammasome activation involves the formation of high-order structures, particularly helical filaments.
  • These filaments are nucleated by upstream signaling molecules.
  • Stoichiometric complexes are less prevalent than dynamic filament assembly during activation.

Conclusions:

  • High-resolution structures provide critical insights into AIM2 inflammasome assembly and regulation.
  • Helical filament formation is a prominent feature across multiple steps of AIM2 inflammasome activation.
  • Understanding these structural mechanisms is crucial for deciphering AIM2 inflammasome function.