Related Experiment Video
Updated: Feb 3, 2026
07:42
Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
8.3K
Role of a Small Molecule in the Modulation of Cell Death Signal Transduction Pathways
Stella Hartmann1, David J Nusbaum2, Kevin Kim1
1School of Applied Life Sciences , Keck Graduate Institute , 535 Watson Drive , Claremont , California 91711 , United States.
ACS Infectious Diseases
|October 26, 2018
Summary
DN1, a novel small molecule, protects cells from anthrax lethal toxin (LT) and other pathogens. It works by modulating G protein-coupled receptor signaling, offering a new tool to study cell death pathways.
Area of Science:
- Immunology
- Pharmacology
- Toxicology
Background:
- Inflammasomes and caspase-1 are key in innate immunity against pathogens.
- Anthrax lethal toxin (LT) causes cytotoxicity via pyroptosis, a form of programmed cell death.
- A small molecule, DN1, was previously found to reduce LT cytotoxicity.
Purpose of the Study:
- To investigate the mechanism by which DN1 reduces LT-induced cytotoxicity.
- To explore DN1's potential as a chemical probe for studying cell death pathways.
Main Methods:
- Cell-based assays to assess DN1's effect on LT cytotoxicity.
- Investigating DN1's impact on LT internalization, catalytic activity, and caspase-1 activation.
- Analyzing DN1's interaction with host cathepsin B and G protein-coupled receptors (GPCRs).
Main Results:
- DN1 protected cells from LT regardless of LT concentration and reduced pathogenicity of other toxins and viruses.
- DN1 did not inhibit LT internalization, catalytic activity, or caspase-1 activation.
- DN1 targets GPCRs, and inhibiting downstream signaling synergized with DN1 to protect cells.
Conclusions:
- DN1 likely reduces LT-induced pyroptosis by antagonizing GPCRs and modulating downstream signal transduction.
- DN1 demonstrated efficacy in reducing susceptibility to toxin-associated bacterial infections in Drosophila melanogaster.
- DN1 serves as a valuable chemical probe for investigating host cell death mechanisms induced by pathogenic agents.
More Related Videos
10:13A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells
Published on: July 3, 2013
11.6K
11:31Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa
Published on: June 30, 2016
9.2K
Related Concept Videos
01:26Signal Transduction: Overview
11.5K
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...
11.5K
01:17Role of ER in the Secretory Pathway
7.1K
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
7.1K
03:14Notch Signaling Pathway
6.6K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.6K
02:33Hedgehog Signaling Pathway
10.1K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
10.1K
01:19Interactions Between Signaling Pathways
7.4K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.4K
01:32Types of Signaling Molecules
13.1K
In multicellular organisms, many molecules transmit signals between cells to pass information. These signals vary in complexity and include small peptides, nucleotides, steroids, fatty acid derivatives, and dissolved gases such as nitric oxide. Some signaling molecules diffuse through the plasma membrane to act locally between neighboring cells or travel long distances. Others remain attached to the cell surface, transmitting information to other cells only when they make contact. In some...
13.1K