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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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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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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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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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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Apoptotic signaling: Beyond cell death.

Maddalena Nano1, Denise J Montell1

  • 1Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, CA 93106, USA; Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA.

Seminars in Cell & Developmental Biology
|November 21, 2023
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Summary

Cells can escape programmed cell death (apoptosis) through specific mechanisms. This study reveals how feedback, dynamics, and noise influence this process, revising our understanding of apoptosis in health and disease.

Keywords:
AnastasisApoptosisCaspaseFeedback in apoptosisRegulated cell death

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Area of Science:

  • Cellular Biology
  • Biochemistry
  • Developmental Biology

Background:

  • Apoptosis, a form of regulated cell death, was traditionally viewed as an irreversible process.
  • Recent findings suggest that cells may possess mechanisms to evade the activation of cell death pathways.

Purpose of the Study:

  • To investigate the molecular mechanisms enabling cells to escape from self-amplifying apoptotic signaling.
  • To analyze the roles of feedback, dynamics, propagation, and noise in apoptotic signaling pathways.
  • To propose a revised model for the function of apoptosis in animal development, homeostasis, and disease.

Main Methods:

  • Analysis of apoptotic signaling pathways.
  • Mathematical modeling of cell death dynamics.
  • Examination of feedback loops and stochastic effects (noise) in cell signaling.

Main Results:

  • Identified key regulatory mechanisms that allow cells to escape irreversible apoptosis.
  • Demonstrated the significant influence of feedback, signal dynamics, propagation, and noise on cell fate decisions.
  • Provided evidence for the dynamic and context-dependent nature of apoptosis.

Conclusions:

  • Apoptosis is not always irreversible; cells can actively escape death signaling.
  • A revised model incorporating dynamic and stochastic elements is proposed for apoptosis.
  • Understanding these escape mechanisms is crucial for comprehending development, homeostasis, and diseases like cancer.