PERK inhibition rewires translational and CMGC protein kinase networks into an antiviral state
Kracht, M.; Shaban, M. S.; Schuele Weiser, H.; Weber, A.; Meier-Soelch, J.; Dort, F.; Mayr-Buro, C.; Poppe, M.; Karl, N.; Wilhelm, J.; Ziebuhr, J.; Linne, U.
Show abstract
Protein kinases (PKs) are central regulators of cellular signaling, yet only a small fraction of the human kinome is targeted therapeutically, and kinase-substrate relationships remain incompletely defined. Here, we systematically characterize kinome regulation during human coronavirus 229E (HCoV-229E) infection across transcriptomic, translational, proteomic, and phospho-proteomic layers. We reveal that pharmacological inhibition of the ER stress sensor kinase PERK reprograms host protein biosynthesis and phospho-proteomic landscapes, simultaneously blocking viral nucleocapsid phosphorylation and modulating multiple host kinases. This rewiring antagonizes virus-induced translational shutdown, along with pronounced regulation of the CMGC kinase family, a pattern conserved in SARS-CoV and SARS-CoV-2 infected cells. Comparative analyses with PERK depletion distinguish on-target from off-target effects of PERK inhibition. Our findings uncover the kinome-scale consequences of PERK perturbation in coronavirus infection and demonstrate how the polypharmacology of PERK inhibitors can be harnessed to establish a potent antiviral state, revealing new avenues for host-directed antiviral strategies.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A proximity proteomics pipeline with improved reproducibility and throughput 95%
- Turnover and replication analysis by isotope labeling (TRAIL) reveals the influence of tissue context on protein and organelle lifetimes 94%
- Systematic identification of structure-specific protein-protein interactions 94%
Similar papers in this journal
Similar papers in this journal
- Dynamics of SARS-CoV-2 host cell interactions inferred from transcriptome analyses 96%
- Pinpointing of cysteine oxidation sites in vivo by high-resolution proteomics reveals mechanism of redox-dependent inhibition of STING 94%
- Non-self RNA rewires IFNβ signaling: A mathematical model of the innate immune response 94%
Similar papers in this journal
- Inhibiting coronavirus replication in cultured cells by chemical ER stress 97%
- Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities 96%
- Pathogenic mutations of human phosphorylation sites affect protein-protein interactions 95%
Similar papers in this journal
- Antagonism of PP2A is an independent and conserved function of HIV-1 Vif and causes cell cycle arrest 96%
- Antiviral function and viral antagonism of the rapidly evolving dynein activating adapter NINL 96%
- A Bidirectional Switch in the Shank3 Phosphorylation State Biases Synapses toward Up or Down Scaling 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.