Related Experiment Video

Updated: Sep 12, 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

c-E10 is a caspase-recruiting domain-containing protein that interacts with components of death receptors signaling

A Costanzo1, C Guiet, P Vito

  • 1Fondazione A. Cesalpino, I Clinica Medica, V.le Policlinico 155, 00161 Roma, Italy.

The Journal of Biological Chemistry
|July 10, 1999
PubMed

Insights

We discovered a novel protein, c-E10, that acts as an adapter protein. It activates NF-kappaB signaling through a pathway linked to death receptor signaling, impacting cell growth and differentiation.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Immunology

Background:

  • Tumor necrosis factor receptor superfamily members regulate apoptosis and cell growth.
  • Death receptor signaling involves interactions with FADD, TRADD, and TRAFs.
  • Novel molecules in death receptor pathways are crucial for understanding cellular regulation.

Purpose of the Study:

  • To identify novel proteins involved in death receptor signaling.
  • To characterize the function of a newly identified protein, c-E10.
  • To elucidate the role of c-E10 in NF-kappaB activation.

Main Methods:

  • Screening for regulatory molecules in death receptor signaling.
  • Transfection experiments to study protein interactions and oligomerization.
  • Doxycycline-inducible expression system to analyze NF-kappaB activation.

Main Results:

  • A novel CARD-containing protein, c-E10, was identified.
  • c-E10 oligomerizes, binds to TRAIL receptor 1 (DR4), and interacts with TRADD.
  • c-E10 expression activates NF-kappaB, inhibited by dominant-negative TRAF2 and NIK kinase.

Conclusions:

  • c-E10 functions as an adapter protein in death receptor signaling.
  • c-E10 activates NF-kappaB through a pathway involving TRADD, TRAF2, and NIK.
  • This finding provides new insights into the regulation of cell growth and differentiation via death receptor pathways.

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

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry05:29

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry

Published on: March 24, 2023

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

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 heterodimer of NF-κB...
Apoptosis01:30

Apoptosis

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.
Caspases01:24

Caspases

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 cells.
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...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...