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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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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...
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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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Overview of Cell Death01:30

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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
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Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
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Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
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Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
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Apoptosis initiation through the cell-extrinsic pathway.

Pradeep Nair1, Min Lu1, Sean Petersen1

  • 1Cancer Immunology, Genentech, Inc., San Francisco, California, USA.

Methods in Enzymology
|June 30, 2014
PubMed
Summary
This summary is machine-generated.

Apoptosis, or programmed cell death, eliminates harmful cells via intrinsic or extrinsic pathways. Death receptor signaling dictates outcomes like apoptosis, necroptosis, or inflammation, crucial for development and homeostasis.

Keywords:
Apo2L/TRAILCaspase-8Cullin 3Death receptorFAADFasL/CD95LNecroptosisTNFUbiquitinationcFLIP

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Apoptosis is a regulated cell death process essential for metazoan development and tissue homeostasis.
  • Caspases are key enzymes initiating and executing apoptosis.
  • Two primary pathways, cell-intrinsic and cell-extrinsic, activate caspases.

Purpose of the Study:

  • To elucidate the mechanisms of apoptosis and death receptor signaling.
  • To explore the diverse cellular outcomes regulated by death receptor pathways.
  • To highlight the homeostatic roles of death receptor signaling.

Main Methods:

  • Review of intrinsic and extrinsic apoptosis signaling pathways.
  • Analysis of caspase activation mechanisms.
  • Examination of death receptor ligand presentation and cellular responses.

Main Results:

  • Cell-intrinsic pathway involves internal distress sensors and Bcl-2 family proteins.
  • Cell-extrinsic pathway utilizes extracellular ligands and death receptors.
  • Ligand presentation mode influences cellular outcomes, including apoptosis, necroptosis, and inflammation.

Conclusions:

  • Death receptor signaling is tightly regulated, impacting cellular fate.
  • This signaling plays vital homeostatic roles throughout embryonic development and adult life.
  • Understanding these pathways is critical for controlling cell death and inflammation.