Targeting protein–protein interactions with reversible covalent modalities: Non‐cysteine chemistries
Abstract Protein–protein interactions (PPIs) are central to diverse cellular functions, and represent a rapidly expanding class of therapeutic targets. Advancements in covalent drug design have enabled small‐molecule drugs to overcome challenges associated with engaging these targets, such as limited durations of action and difficult‐to‐drug (expansive,
Ruchira Basu, Steven Fletcher
wiley +1 more source
MYC drives nelarabine resistance in T‐ALL via a hyperactive transcriptional program. Pharmacological degradation of BET proteins dismantles this addiction, restoring drug sensitivity and extending survival in vivo. ABSTRACT Acquired resistance represents a fundamental obstacle limiting the long‐term efficacy of cancer chemotherapy.
Jingjing Gao +9 more
wiley +1 more source
Intrinsic specificity of a ‘core’ TIP60 acetyltransferase complex in Drosophila
The intrinsic substrate selectivity of the Drosophila TIP60‐core acetyltransferase was determined using synthetic nucleosome arrays. Targeted mass spectrometry revealed site‐specific acetylation of histones H2A, H2A.V, and H4, uncovering distinct acetylation rates and patterns across individual lysines.
Silke Krause +5 more
wiley +1 more source
The competitive interplay of 12‐oxophytodienoic acid (OPDA), protein thiols, and glutathione
12‐Oxophytodienoic acid (OPDA) is a phytohormone involved in plant growth and stress defense. Due to its cyclopentenone moiety, OPDA can form Michael adducts with thiol‐containing compounds such as glutathione and cysteine residues of proteins, resulting in alterations of the cellular redox regulatory network.
Madita Knieper +8 more
wiley +1 more source
Degradomics for large‐scale mechanistic insights on proteases and proteolysis in human health
Proteolysis has an important role in human disease but remains relatively unexplored. Degradomics, the uncovering of proteolysis in tissues, cells, and proteins, uses mass spectrometry‐based terminomics to identify protein termini occurring therein (forward degradomics) and to define the actions of proteases (reverse degradomics).
Daniel R. Martin +2 more
wiley +1 more source
Post‐transcriptional regulatory networks: The dynamic interplay of RNA‐binding proteins
Post‐transcriptional gene expression regulation is controlled by RNA‐binding proteins (RBPs), which influence many processes including splicing, localization, translation, and decay. Rather than acting alone, RBPs bind RNAs combinatorially, forming complex, context‐dependent regulatory networks.
Lena A. Street +2 more
wiley +1 more source
Mass spectrometry analysis of transthyretin (TTR) post-translational modifications (PTMs) in hereditary ATTR: a case-control Spanish experience [PDF]
Vilà-Rico M +7 more
europepmc +1 more source
Spatially resolved mapping of histones reveals selective neuronal response in Rett syndrome
Loss of Mecp2 function is associated with Rett syndrome (RTT). MeCP2 regulates chromatin, yet its influence on histone composition and dynamics is unclear. Combining MALDI‐MSI with LCM–LC–MS/MS, we mapped histone proteoforms across the dentate gyrus, cornu ammonis, and cerebellum in two mouse models of RTT.
Frederike Schäfer +6 more
wiley +1 more source
Biogenesis of TNF‐α‐insights into proteostasis and inflammation
TNF‐α biogenesis, trafficking, and signalling are tightly and reciprocally coupled to cellular proteostasis systems, including ER chaperones and endoplasmic reticulum‐associated degradation. This bidirectional crosstalk determines whether TNF‐α responses are adaptive or proteotoxic.
Bailasan Haidar +3 more
wiley +1 more source
Autoimmunity and Periodontitis
In a microbe‐driven inflammatory environment, peptidyl‐arginine deiminase (PAD) enzymes from neutrophils and Porphyromonas gingivalis citrullinate both microbial and self‐antigens. B cell presentation of citrullinated or self‐mimicking epitopes activates T cells that assist B cells in antibody isotype switching, affinity maturation, epitope spreading ...
Massimo Costalonga +2 more
wiley +1 more source

