Redox Signaling by Reactive Electrophiles and Oxidants

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Redox homeostasis is a key factor in maintaining cellular function and health. The main determinant of the intracellular redox potential is ubiquitous glutathione (GSH) together with its oxidized dimer (GSSG). Importantly, both redox equilibrium and GSH ho ...

Localized sources of morphogens, called signalling centres, play a fundamental role in coordinating tissue growth and cell fate specification during organogenesis. However, how these signalling centres are established in tissues during embryonic developmen ...

Glutathione (GSH) is the main determinant of intracellular redox potential and participates in multiple cellular signalling pathways. Achieving a detailed understanding of intracellular GSH homeostasis depends on the development of tools to map GSH compart ...

Chimeric antigen receptors (CARs) are synthetic, transmembrane proteins that trigger immune cell signaling following their engagement. They have been first utilized in T cells and later in natural killer (NK) cells to redirect their cytotoxicity toward a s ...

Native reactive electrophile species (RES) such as 4-hydroxynonenal (HNE) act as cellular signals through covalent modification of kinetically-privileged electrophile sensor proteins. Research efforts in the field focus mainly on identifying these sensor p ...

Reactive metabolites and related electrophilic drugs are among the most challenging small molecules to study. Conventional approaches to deconstruct the mode of action (MOA) of such molecules leverage bulk treatment of experimental specimens with an excess ...

Telomeres are nucleoprotein structures at the ends of linear chromosomes, being essential for the maintenance of genomic integrity. Telomeres have a unique structure which distinguishes chromosome termini from DNA damage sites. Shelterin complexes are the ...

Cell-cell communication is fundamental for immune balance. Multivalent interactions of surface receptors at immune interfaces drive specific communication, with stimulatory and inhibitory signals guiding the immune outcome. Notably, the valency, affinity, ...

Glucose sensing in pancreatic D-cells depends on oxidative phosphorylation and mitochondria-derived signals that promote insulin secretion. Using mass spectrometry-based phosphoproteo-mics to search for downstream effectors of glucose-dependent signal tran ...

Our bodies produce a host of electrophilic species that can label specific endogenous proteins in cells. The signaling roles of these molecules are under active debate. However, in our opinion, it is becoming increasingly likely that electrophiles can rewi ...

Oxidative stress is a natural phenomenon in the body. Under physiological conditions intracellular reactive oxygen species (ROS) are normal components of signal transduction cascades, and their levels are maintained by a complex antioxidants systems partic ...

For several years, drugs with reactive electrophilic appendages have been developed. These units typically confer prolonged residence time of the drugs on their protein targets, and may assist targeting shallow binding sites and/or improving the drug-prote ...

Redox signaling events mediated by reactive electrophilic species (RES) are key players in several cellular processes. However, the studies on RES have been challenging due to their high reactivity towards numerous nucleophilic groups present in the cells ...

G protein-coupled receptors (GPCRs) are 7-transmembrane alpha-helical integral membrane proteins on which cells heavily rely to receive information regarding their external environment. These receptors are able to transfer information to intracellular down ...

Redox homeostasis is essential for cell function and its disruption is associated with multiple pathologies. Redox balance is largely regulated by the relative concentrations of reduced and oxidized glutathione. In eukaryotic cells, this ratio is different ...

The careful design of the antibody architecture is becoming more and more important, especially when the purpose is agonism. We present the design of a novel antibody format that is able to promote receptor dimerization and induce signal transduction resul ...

It is now clear that some cysteines on some proteins are highly tuned to react with electrophiles. Based on numerous studies, it is also established that electrophile sensing underpins rewiring of several critical signaling processes. These electrophile-se ...

Plant reproduction relies on the highly regulated growth of the pollen tube for sperm delivery. This process is controlled by secreted RALF signaling peptides, which have previously been shown to be perceived by Catharanthus roseus RLK1-like (CrRLK1Ls) mem ...

Cancer is a leading cause of death in the world, and the mechanisms that underlie this disease are still not completely understood. As cancer develops and progresses, cells undergo a diversity of mutations that sustain their rapid proliferation and the eva ...

Recent Advances: Herein, we focus on the first step of this process, electrophile sensing. Electrophile sensing is typically a deceptively simple reaction between the thiol of a protein cysteine, of which there are around 200,000 in the human proteome, and ...

Redox Signaling by Reactive Electrophiles and Oxidants

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HaloTag-Based Tools for Live-Cell Imaging and Elucidation of Organellar Redox Biology

Proliferation-driven mechanical compression induces signalling centre formation during mammalian organ development

A locally activatable sensor for robust quantification of organellar glutathione

Unlocking Hidden Potential: Exploring the Complexities of Signaling in Immune Cell Activation to Optimize CAR Therapy

Towards Uncovering the Mechanisms of Electrophile Sensing and Signaling

Monitoring On-Target Signaling Responses in Larval Zebrafish- Z-REX Unmasks Precise Mechanisms of Electrophilic Drugs and Metabolites

Telomere protection against oxidative stress

Exploring the interplay of molecular pattern and valency for selective interactions at the bio-interface

SLC25A46 promotes mitochondrial fission and mediates resistance to lipotoxic stress in INS-1E insulin-secreting cells

Hitting the Bullseye: Endogenous Electrophiles Show Remarkable Nuance in Signaling Regulation

Overview of oxidative stress findings in hepatic encephalopathy: From cellular and ammonium-based animal models to human data

Can Precision Electrophile Signaling Make a Meaningful and Lasting Impression in Drug Design?

Method Development towards Orthogonal Electrophile Delivery

Reprogramming G Protein-Coupled Receptor Structure, Function And Signaling By Computational Design

Disruption of mitochondrial redox homeostasis by enzymatic activation of a trialkylphosphine probe

The Contorsbody, an antibody format for agonism: design, structure, and function

REX technologies for profiling and decoding the electrophile signaling axes mediated by Rosetta Stone proteins

Structural basis for recognition of RALF peptides by LRX proteins during pollen tube growth

Modeling metabolic and signaling pathways in cancer cells

Getting the Right Grip? How Understanding Electrophile Selectivity Profiles Could Illuminate Our Understanding of Redox Signaling