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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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Membrane Asymmetry Regulating Transporters01:19

Membrane Asymmetry Regulating Transporters

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Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
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Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

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Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
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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

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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Apoptosis01:30

Apoptosis

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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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Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
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FLIP(L): the pseudo-caspase.

Peter Smyth1, Tamas Sessler1, Christopher J Scott1

  • 1The Patrick G Johnston Centre for Cancer Research, Queen's University, Belfast, UK.

The FEBS Journal
|February 26, 2020
PubMed
Summary
This summary is machine-generated.

FLIP(L) is the sole human pseudo-caspase, regulating apoptosis and inflammation. This review explores its canonical roles in caspase-8 modulation and nonclassical functions beyond cell death regulation.

Keywords:
DISCFLIP(L)apoptosisautophagycaspasenecroptosispseudo-caspasepseudoenzymes

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Pseudoenzymes share structural homology with active enzymes but lack catalytic activity.
  • Caspases are critical proteases involved in cell death and inflammation.
  • FLIP(L) is the only known human pseudo-caspase and a paralog of caspase-8 and caspase-10.

Purpose of the Study:

  • To review the canonical roles of FLIP(L) in modulating caspase-8 activity and apoptotic signaling.
  • To describe the nonclassical, caspase-8-independent functions of FLIP(L).

Main Methods:

  • Literature review of studies on FLIP(L) function.
  • Analysis of FLIP(L)'s interactions with caspases and signaling pathways.

Main Results:

  • FLIP(L) regulates caspase-8 processing and activity, impacting signaling via death receptors, TNFR1, and Toll-like receptors.
  • FLIP(L) exhibits nonclassical pseudoenzyme functions independent of caspase-8.
  • These functions contribute to diverse biological processes beyond cell death.

Conclusions:

  • FLIP(L) plays a dual role: a canonical modulator of caspase-8-mediated apoptosis and inflammation, and a nonclassical regulator of various cellular processes.
  • Understanding FLIP(L)'s multifaceted functions is crucial for comprehending cell death and other biological pathways.