ArticleCell host & microbe2017
Inhibiting the Plasmodium eIF2α Kinase PK4 Prevents Artemisinin-Induced Latency.
Article in Cell host & microbe, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.
- Ubiquitin-proteasome system inFrontiers in medicine · 2024Pooled it
- The long and winding road: On the endoplasmic reticulum of Plasmodium and implications for pathogenesis.PLoS pathogens · 2026Review
- Ligand decorated nanostructure carrier systems for targeted delivery of antimalarials.Discover nano · 2026Review
- The integrated stress response in apicomplexan and trypanosomatid parasites: balancing survival and pathogenesis.Frontiers in immunology · 2026Review
- PfPI3K inhibition reversed artemisinin resistance by increasing ROS and ubiquitinated protein levels in Plasmodium falciparum.Communications biology · 2025Article
- Article
- Biochemical and biophysical characterization of Plasmodium falciparum glucose regulated protein 170.Scientific reports · 2025Article
- NOXA exacerbates endoplasmic-reticulum-stress-induced intervertebral disc degeneration by activating apoptosis and ECM degradation.Cell death discovery · 2025Article
- PfPPM2 signalling regulates asexual division and sexual conversion of human malaria parasite Plasmodium falciparum.Nature communications · 2025Article
- Endoplasmic Reticulum Stress: Implications in Diseases.The protein journal · 2025Review
- Unraveling the Role of Proteinopathies in Parasitic Infections.Biomedicines · 2025Review
- Monitoring molecular markers associated with antimalarial drug resistance in south-east Senegal from 2021 to 2023.The Journal of antimicrobial chemotherapy · 2025Article
- Endoplasmic reticulum stress in lung cancer.Frontiers in oncology · 2025Review
- Artemisinin-resistant malaria.Clinical microbiology reviews · 2024Review
- Enhanced cell stress response and protein degradation capacity underlie artemisinin resistance inmSphere · 2024Article
- Artemisinin-resistant Plasmodium falciparum Kelch13 mutant proteins display reduced heme-binding affinity and decreased artemisinin activation.Communications biology · 2024Article
- Functional Characterization of Six Eukaryotic Translation Initiation Factors ofInternational journal of molecular sciences · 2024Article
- Impact of different mutations on Kelch13 protein levels, ART resistance, and fitness cost inmBio · 2024Article
- tRNA modification reprogramming contributes to artemisinin resistance in Plasmodium falciparum.Nature microbiology · 2024Article
- The DEAD-box RNA helicase PfDOZI imposes opposing actions on RNA metabolism in Plasmodium falciparum.Nature communications · 2024Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
9 authors at 6 institutions in 1 country.
Funding
Abstract
Artemisinin and its derivatives (ARTs) are frontline antimalarial drugs. However, ART monotherapy is associated with a high frequency of recrudescent infection, resulting in treatment failure. A subset of parasites is thought to undergo ART-induced latency, but the mechanisms remain unknown. Here, we report that ART treatment results in phosphorylation of the parasite eukaryotic initiation factor-2α (eIF2α), leading to repression of general translation and latency induction. Enhanced phosphorylated eIF2α correlates with high rates of recrudescence following ART, and inhibiting eIF2α dephosphorylation renders parasites less sensitive to ART treatment. ART-induced eIF2α phosphorylation is mediated by the Plasmodium eIF2α kinase, PK4. Overexpression of a PK4 dominant-negative or pharmacological inhibition of PK4 blocks parasites from entering latency and abolishes recrudescence after ART treatment of infected mice. These results show that translational control underlies ART-induced latency and that interference with this stress response may resolve the clinical problem of recrudescent infection.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.