Related Experiment Video
Updated: Jul 1, 2026
06:12
LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation
Published on: May 3, 2024
The extrinsic cell death pathway and the élan mortel
D Wallach1, T-B Kang, A Kovalenko
1Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel. d.wallach@weizmann.ac.il
Cell Death and Differentiation
|September 17, 2008
Summary
Proteins involved in cell death signaling, like caspase-8, also perform other functions. Understanding this dual role may reveal specific protein structures responsible for cell death induction.
Area of Science:
- Molecular Biology
- Immunology
- Cell Biology
Background:
- Historically, a 'vital force' was thought to differentiate organic from inorganic molecules.
- Early research on cell death suggested death-signaling molecules possess exclusive lethal functions.
- Initial understanding of intracellular death-signaling proteins implied dedicated death-related roles.
Purpose of the Study:
- To challenge the notion that death-signaling proteins have solely death-related functions.
- To investigate the non-death-related roles of proteins involved in cell death induction.
- To identify structural determinants conferring death specificity in multifunctional proteins.
Main Methods:
- Review of historical scientific beliefs regarding vital forces.
- Analysis of early concepts on cytotoxic cell-mediated death.
- Examination of intracellular protein functions in cell death pathways.
- Case study focusing on caspase-8's dual signaling roles.
Main Results:
- Proteins mediating cell death induction also exhibit non-death-related functions.
- Caspase-8 exemplifies proteins with both extrinsic cell-death pathway activation and non-death roles.
- Evidence suggests a functional divergence within death-induction proteins.
Conclusions:
- The exclusive dedication of death-signaling molecules to lethal tasks is being re-evaluated.
- Investigating the mechanistic basis of protein functional heterogeneity is crucial.
- Identifying specific structural elements may distinguish death-specific functions of proteins like caspase-8.
Related Concept Videos
01:17The 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...
01:30Overview of Cell Death
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.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
01:30Apoptosis
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.
01:31The 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...
01:11Cellular Injury IlI: Cellular Death
Cell death is the irreversible loss of cellular structure and function, representing the final stage of severe injury. It plays a key role in both normal physiology and disease.Types of Cell DeathThe two main types are necrosis and apoptosis, though others like necroptosis and pyroptosis also exist.Necrosis:Necrosis is an unregulated form of cell death caused by severe injury such as trauma, toxins, or ischemia. It is characterized by cell swelling, membrane loss, rupture, and leakage of...
01:16Necrosis
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...