Daraxonrasib and Beyond: Pan‐RAS Inhibition, Resistance, and Next‐Generation Strategies
Cancer Science, EarlyView.ABSTRACT RAS proteins have long been considered difficult therapeutic targets, but allele‐selective inhibitors established the clinical tractability of mutant RAS. Daraxonrasib (RMC‐6236), an oral pan‐RAS inhibitor, has now extended this concept by targeting multiple mutant and wild‐type RAS proteins.
Ryo Honda
wiley +1 more source
Macrophage Lipid Homeostasis Drives IVDD via a Senescence‐Dependent Impairment of Efferocytosis
Cell Proliferation, EarlyView.Intervertebral disc degeneration (IVDD) has been a leading cause of low back pain and lacks disease‐modifying therapies. Although dysregulated disc lipid metabolism is implicated, its impact on the immune microenvironment, particularly macrophages, remains unknown.
Jinyu Wang +12 more
wiley +1 more source
GCN2 in proteostasis: structural logic, signalling networks and disease
The FEBS Journal, EarlyView.Threats to protein synthesis activate the kinase GCN2, initiating the integrated stress response (ISR). GCN2 is triggered by stalled ribosomes and uncharged tRNAs, which accumulate when amino acids are scarce. The ISR adjusts cellular physiology by promoting redox balance, protein quality control, and mitochondrial optimisation.
JiaYi Zhu, Stefan J. Marciniak
wiley +1 more source
The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits
International Journal of Biological Sciences, 2005 The heterotrimeric G-protein alpha subunit has long been considered a bimodal, GTP-hydrolyzing switch controlling the duration of signal transduction by seven-transmembrane domain (7TM) cell-surface receptors.
doaj
Rab21 recruits EEA1 and competes with Rab5 for Rabex-5 activation
Frontiers in Cell and Developmental BiologyRab5 is a key regulator of early endosomal traffic and fusion. It shares its localization and guanine nucleotide exchange factor Rabex-5 with the less characterized member of the Rab5 subfamily Rab21.
Francisco Yanguas, Cinzia Progida
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Identification of guanine nucleotide exchange factors that increase Cdc42 activity in primary human endothelial cells. [PDF]
Small GTPases, 2021 Reinhard NR +6 more
europepmc +1 more source
RNF13 regulates the endolysosomal pathway through interaction with the small GTPase Arl8B
The FEBS Journal, EarlyView.The E3 ubiquitin ligase RNF13 functions as a regulatory scaffold, organizing Arl8B‐dependent complexes and tuning downstream signaling that controls endolysosomal organization and trafficking. In this model, wild‐type RNF13 associates with Arl8B on endolysosomes, whereas Arl8B (E22D/F55A) or RNF13 (L244A) variants weaken complex assembly, potentially ...
Audrey M. Sénécal +4 more
wiley +1 more source
Elevated cAMP Protects against Diclofenac-Induced Toxicity in Primary Rat Hepatocytes: A Protective Effect Mediated by the Exchange Protein Directly Activated by cAMP/cAMP-Regulated Guanine Nucleotide Exchange Factors. [PDF]
Mol Pharmacol, 2021 Aguilar Mora FA +7 more
europepmc +1 more source
Insect Molecular Biology, EarlyView.RNA‐seq and Batelli gland proteomics of fifth‐instar Mahanarva spectabilis nymphs reveal transcripts and proteins associated with xylem feeding, foam production and environmental interaction. Functional annotation identified genes involved in osmoregulation, detoxification, chemosensation and stress responses, while proteomic analysis confirmed ...
Monique da Silva Bonjour +8 more
wiley +1 more source