ArticlePLoS genetics2019
Cellular response to small molecules that selectively stall protein synthesis by the ribosome.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Halting translation by the letter with sequence-selective small molecules.Nature chemical biology · 2026Review
- The GENEVA platform models tumor mosaicism to reveal variations of responses to KRAS inhibitors and identify improved drug combinations.Nature cancer · 2026Article
- The ribosome ubiquitination code: fine-tuning translation under stress.Trends in biochemical sciences · 2025Review
- Sensitivity to an inhibitor of translation elongation in solid and hematologic cancers.Scientific reports · 2025Article
- SVC112: From Hummingbirds to Head and Neck Cancer.Advances in experimental medicine and biology · 2025Article
- LVING reveals the intracellular structure of cell growth.Scientific reports · 2024Article
- System-wide analysis of RNA and protein subcellular localization dynamics.Nature methods · 2024Article
- A highly efficient human cell-free translation system.RNA (New York, N.Y.) · 2023Article
- A highly efficient human cell-free translation system.bioRxiv : the preprint server for biology · 2023Article
- Article
- Eukaryotic ribosome quality control system: a potential therapeutic target for human diseases.International journal of biological sciences · 2022Review
- Inhibition of the Eukaryotic 80S Ribosome as a Potential Anticancer Therapy: A Structural Perspective.Cancers · 2021Review
- HectD1 controls hematopoietic stem cell regeneration by coordinating ribosome assembly and protein synthesis.Cell stem cell · 2021Article
- Article
- Chronic exposure to the gibberellin derivative GA-13315 sensitizes breast cancer MCF-7 cells but not colon cancer HCT116 cells to irinotecan.Oncology letters · 2020Article
- Ribosome-associated quality control of membrane proteins at the endoplasmic reticulum.Journal of cell science · 2020Review
- SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses.Cell · 2020Article
- The interaction of DNA repair factors ASCC2 and ASCC3 is affected by somatic cancer mutations.Nature communications · 2020Article
- A Quick Guide to Small-Molecule Inhibitors of Eukaryotic Protein Synthesis.Biochemistry. Biokhimiia · 2020Review
- Selective inhibition of human translation termination by a drug-like compound.Nature communications · 2020Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Identifying small molecules that inhibit protein synthesis by selectively stalling the ribosome constitutes a new strategy for therapeutic development. Compounds that inhibit the translation of PCSK9, a major regulator of low-density lipoprotein cholesterol, have been identified that reduce LDL cholesterol in preclinical models and that affect the translation of only a few off-target proteins. Although some of these compounds hold potential for future therapeutic development, it is not known how they impact the physiology of cells or ribosome quality control pathways. Here we used a genome-wide CRISPRi screen to identify proteins and pathways that modulate cell growth in the presence of high doses of a selective PCSK9 translational inhibitor, PF-06378503 (PF8503). The two most potent genetic modifiers of cell fitness in the presence of PF8503, the ubiquitin binding protein ASCC2 and helicase ASCC3, bind to the ribosome and protect cells from toxic effects of high concentrations of the compound. Surprisingly, translation quality control proteins Pelota (PELO) and HBS1L sensitize cells to PF8503 treatment. In genetic interaction experiments, ASCC3 acts together with ASCC2, and functions downstream of HBS1L. Taken together, these results identify new connections between ribosome quality control pathways, and provide new insights into the selectivity of compounds that stall human translation that will aid the development of next-generation selective translation stalling compounds to treat disease.
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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 Socratic graph.