Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Disassembly of Intermediate Filaments01:35

Disassembly of Intermediate Filaments

2.1K
Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
2.1K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

6.6K
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...
6.6K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

6.8K
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...
6.8K
Assembly of Cytoskeletal Filaments01:18

Assembly of Cytoskeletal Filaments

21.4K
Cytoskeletal filaments are polymeric forms of smaller protein subunits. However, individual cytoskeletal filaments may easily disassemble or associate with other similar filaments to form rigid structures. Microfilaments, made of actin monomers, rely on actin-binding proteins to form bundles and create networks of individual actin filaments. Microtubules rely on microtubule-associated proteins (MAPs) to form sturdy cylindrical structures. However, the proteins involved in forming complex...
21.4K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

7.8K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.8K
Protein Complex Assembly02:41

Protein Complex Assembly

10.8K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types.  Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
10.8K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Distinct RNA engagements define genome import and replication elongation in alphaviruses.

bioRxiv : the preprint server for biology·2026
Same author

A self-amplifying RNA vector based on rubella virus for mRNA therapeutics and vaccine applications.

Molecular therapy. Nucleic acids·2026
Same author

DDX6 induces immunosuppression in cancer by disrupting structural stability of endogenous double-stranded RNAs.

Science immunology·2026
Same author

Cryo-EM structures of anti Z-DNA antibodies in complex with antigen reveal distinct recognition modes of a left-handed geometry.

Nucleic acids research·2026
Same author

Conservation of Bacterial Lipopolysaccharide Binding by SARS-CoV-2 Spike across Major Viral Variants.

Computational and structural biotechnology journal·2026
Same author

Discovery of a potent anti-Zika virus benzamide series targeting the viral protein NS4B.

PLoS pathogens·2026

Related Experiment Video

Updated: Sep 10, 2025

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
07:17

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

Published on: August 2, 2021

2.6K

FADDDED filaments coordinate complex IIa assembly during TNF-induced apoptosis.

Ying Chen1, Vinh Thang Huynh1, Lihua Lai1

  • 1Laboratory of NF-κB Signalling, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore.

Proceedings of the National Academy of Sciences of the United States of America
|August 21, 2025
PubMed
Summary

The study reveals that FADD death effector domain (DED) filaments are crucial for initiating extrinsic apoptosis by facilitating RIPK1 and caspase-8 recruitment. This filament formation is essential for TNF-induced cell death and reveals new insights into cFLIP

Keywords:
FADDRIPK1TNFR1extrinsic apoptosisfilament

More Related Videos

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

9.1K
A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

9.2K

Related Experiment Videos

Last Updated: Sep 10, 2025

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
07:17

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

Published on: August 2, 2021

2.6K
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

9.1K
A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

9.2K

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Extrinsic apoptosis is triggered by death receptors, assembling RIPK1, FADD, and caspase-8.
  • Caspase-8 activation involves filament formation via its tandem death effector domain (tDED).
  • The oligomeric structure and function of FADD's DED (FADDDED) in apoptosis are not well understood.

Purpose of the Study:

  • To elucidate the structural basis of FADDDED filament formation.
  • To investigate the role of FADDDED filamentation in extrinsic apoptosis initiation.
  • To uncover novel mechanisms of cFLIP in regulating apoptosis.

Main Methods:

  • Cryogenic-electron microscopy (cryo-EM) to determine the structure of FADDDED filaments.
  • Site-directed mutagenesis to assess the functional impact of filament disruption.
  • Molecular dynamics simulations to analyze protein-protein interactions and thermodynamic preferences.

Main Results:

  • FADDDED filaments form three-helical chains stabilized by iterative interactions.
  • Disruption of FADDDED filaments impairs RIPK1/caspase-8 recruitment and abrogates TNF-induced apoptosis.
  • FADDDED filamentation is required for RIPK1-FADD interaction and is antagonized by cFLIP.

Conclusions:

  • FADDDED filament formation is a critical mechanistic step in TNF-induced extrinsic apoptosis.
  • This process is essential for the assembly of the death-inducing signaling complex (DISC).
  • cFLIP employs an additional anti-apoptotic mechanism by destabilizing FADDDED filaments.