Related Experiment Video

Updated: Aug 5, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

FADD self-association is required for stable interaction with an activated death receptor

C Sandu1, G Morisawa, I Wegorzewska

  • 1Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY 10021, USA.

Cell Death and Differentiation
|May 20, 2006
PubMed

Insights

Programmed cell death relies on the FADD adaptor protein. FADD self-association via its DED domain is essential for forming the death-inducing signaling complex and initiating cell death.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Receptor-mediated programmed cell death is crucial for development and tissue homeostasis.
  • The adaptor protein FADD (Fas-associated death domain) plays a central role in assembling death-inducing signaling complexes (DISCs).
  • FADD recruits initiator procaspases (caspase-8/10) to activated death receptors.

Purpose of the Study:

  • To investigate the role of FADD self-association in DISC formation.
  • To elucidate the structural requirements for FADD's function in programmed cell death.
  • To propose a revised model for FADD signaling complex architecture.

Main Methods:

  • Biochemical dissection of the FADD death effector domain (DED).
  • Functional replacement of DED with engineered oligomerization motifs of defined stoichiometries.
  • Analysis of DISC assembly and competence following disruption of FADD self-association.

Main Results:

  • FADD self-association through its DED is obligatory for DISC assembly.
  • The caspase-recruitment function of FADD can be functionally separated from its self-association.
  • Disruption of FADD self-association prevents the formation of a competent signaling complex.

Conclusions:

  • FADD self-association is a critical prerequisite for initiating programmed cell death.
  • FADD acts as a molecular bridge, organizing activated death receptors into a signaling array.
  • This finding offers a new perspective on the architecture and function of FADD-mediated signaling complexes.

More Related Videos

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

Related Concept Videos

Overview of Cell Death01:30

Overview 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...
The Extrinsic Apoptotic Pathway01:17

The 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...
The Intrinsic Apoptotic Pathway01:31

The 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...
Autophagic Cell Death01:18

Autophagic Cell Death

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.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

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
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

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.
Some...