ATF4‐mediated stress response as a therapeutic vulnerability in chordoma
Molecular Oncology, EarlyView.We screened 5 chordoma cell lines against 100+ inhibitors of epigenetic and metabolic pathways and kinases and identified halofuginone, a tRNA synthetase inhibitor. Mechanistically halofuginone induces an integrated stress response, with eIF2alpha phosphorylation, activation of ATF4 and its target genes CHOP, ASNS, INHBE leading to cell death ...
Lucia Cottone +11 more
wiley +1 more source
Fingolimod mitigates memory loss in a mouse model of Gulf War Illness amid decreasing the activation of microglia, protein kinase R, and NFκB. [PDF]
Neurotoxicology, 2023 Carreras I +4 more
europepmc +1 more source
Molecular Oncology, EarlyView.Pharmacologic ascorbate (vitamin C) increases ROS, disrupts cellular metabolism, and induces DNA damage in CRPC cells. These effects sensitize tumors to PARP inhibition, producing synergistic growth suppression with olaparib in vitro and significantly delayed tumor progression in vivo. Pyruvate rescue confirms ROS‐dependent activity.
Nicolas Gordon +13 more
wiley +1 more source
The adaptor protein CRK is a pro-apoptotic transducer of endoplasmic reticulum stress. [PDF]
, 2011 Excessive demands on the protein-folding capacity of the endoplasmic reticulum (ER) cause irremediable ER stress and contribute to cell loss in a number of cell degenerative diseases, including type 2 diabetes and neurodegeneration.
Austgen, Kathryn +4 more
core
Molecular BrainObjective Cerebral ischemia–reperfusion injury (CIRI) is a major obstacle to neurological recovery after clinical treatment of ischemic stroke. The aim of this study was to investigate the molecular mechanism of Nek6 alleviating CIRI through autophagy ...
Qingzhi Wang +6 more
doaj +1 more source
Astrocytic deletion of protein kinase R-like ER kinase (PERK) does not affect learning and memory in aged mice but worsens outcome from experimental stroke. [PDF]
J Neurosci Res, 2023 Lahiri A +5 more
europepmc +1 more source
LDAcoop: Integrating non‐linear population dynamics into the analysis of clonogenic growth in vitro
Molecular Oncology, EarlyView.Limiting dilution assays (LDAs) quantify clonogenic growth by seeding serial dilutions of cells and scoring wells for colony formation. The fraction of negative wells is plotted against cells seeded and analyzed using the non‐linear modeling of LDAcoop.
Nikko Brix +13 more
wiley +1 more source
Uncharged tRNA Activates GCN2 by Displacing the Protein Kinase Moiety from a Bipartite tRNA-Binding Domain [PDF]
, 2000 Protein kinase GCN2 regulates translation in amino acid–starved cells by phosphorylating eIF2. GCN2 contains a regulatory domain related to histidyl-tRNA synthetase (HisRS) postulated to bind multiple deacylated tRNAs as a general sensor of starvation ...
Anderson, James T. +4 more
core +1 more source
Modelling the impact of protein-kinase R allelic variant on HIV biomarkers trajectories by means of latent class mixed models. [PDF]
Sci Rep, 2022 Brombin C +7 more
europepmc +1 more source
Hepatitis C Virus Blocks Interferon Effector Function by Inducing Protein Kinase R Phosphorylation [PDF]
, 2009 Urtzi Garaigorta, Francis V. Chisari
openalex +1 more source