Evidence map›Paper›PMID 38670073›Full record

ArticleCell2024

Positive selection CRISPR screens reveal a druggable pocket in an oligosaccharyltransferase required for inflammatory signaling to NF-κB.

Benjamin L Lampson, Ana S Ramίrez, Marta Baro, Lixia He, Mudra Hegde, Vidyasagar Koduri, Jamie L Pfaff, Ruth E Hanna, Julia Kowal, Nitin H Shirole and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
12.5field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 44 citations in OpenAlex.

  1. Positive selection screen identifies natural product β-catenin inactivators.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Review
  3. Oncogenic Gα signaling requires AP-3-dependent recruitment to the endolysosomal compartment.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Review
  5. Article
  6. Molecular pharmaceutics · 2026
    Article
  7. Article
  8. Calsyntenin-3 suppresses inflammation via inhibition of TLR N-glycosylation and membrane localization.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Glycosylation in kidney diseases.Precision clinical medicine · 2025
    Review
  19. ER-resident CCDC134 safeguards TLR4 maturation by maintaining gp96 stability.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 2 countries.

Benjamin L LampsonDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
Ana S RamίrezInstitute of Molecular Biology and Biophysics, Eidgenössische Technische Hochschule (ETH), Zürich, Switzerland.
Marta BaroDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Lixia HeDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
Mudra HegdeGenetic Perturbation Platform, Broad Institute, Cambridge, MA 02142, USA.
Vidyasagar KoduriDivision of Hematology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA.
Jamie L PfaffDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
Ruth E HannaGenetic Perturbation Platform, Broad Institute, Cambridge, MA 02142, USA.
Julia KowalInstitute of Molecular Biology and Biophysics, Eidgenössische Technische Hochschule (ETH), Zürich, Switzerland.
Nitin H ShiroleDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
Yanfeng HeDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
John G DoenchGenetic Perturbation Platform, Broad Institute, Cambridge, MA 02142, USA.
Joseph N ContessaDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Kaspar P LocherInstitute of Molecular Biology and Biophysics, Eidgenössische Technische Hochschule (ETH), Zürich, Switzerland. Electronic address: locher@mol.biol.ethz.ch.
William G KaelinDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA. Electronic address: william_kaelin@dfci.harvard.edu.
Dana-Farber Cancer Institute · USBroad Institute · USETH Zurich · CHHarvard University · USYale University · US

Funding

Physician Scientist Training in Cancer ResearchT32CA009172 · NCI · DANA-FARBER CANCER INSTITUTE · PI Jennifer R Brown, James A. DeCaprio · 1985 to 2026
$17.1M
The von Hippel-Lindau Tumor Suppressor Gene and Kidney Cancer: Insights into Oxygen Sensing and Treating Cancers Caused by Undruggable MutationsR35CA210068 · NCI · DANA-FARBER CANCER INST · PI WILLIAM G. KAELIN · 2016 to 2026
$10.8M
OST Inhibition in NSCLCR01CA240418 · NCI · YALE UNIVERSITY · PI CONTESSA, JOSEPH N · 2020 to 2024
$2.4M
Mechanism of Action of Spautin-1, A Novel Degrader of IKZF1K08CA252611 · NCI · DANA-FARBER CANCER INST · PI KODURI, VIDYASAGAR · 2020 to 2024
$1.1M
NCI NIH HHS K08 CA252611NCI NIH HHS R01 CA240418NCI NIH HHS R35 CA210068NCI NIH HHS T32 CA009172
6 · The paper itself

Abstract

Nuclear factor κB (NF-κB) plays roles in various diseases. Many inflammatory signals, such as circulating lipopolysaccharides (LPSs), activate NF-κB via specific receptors. Using whole-genome CRISPR-Cas9 screens of LPS-treated cells that express an NF-κB-driven suicide gene, we discovered that the LPS receptor Toll-like receptor 4 (TLR4) is specifically dependent on the oligosaccharyltransferase complex OST-A for N-glycosylation and cell-surface localization. The tool compound NGI-1 inhibits OST complexes in vivo, but the underlying molecular mechanism remained unknown. We did a CRISPR base-editor screen for NGI-1-resistant variants of STT3A, the catalytic subunit of OST-A. These variants, in conjunction with cryoelectron microscopy studies, revealed that NGI-1 binds the catalytic site of STT3A, where it traps a molecule of the donor substrate dolichyl-PP-GlcNAc

Indexed as

CRISPR-Cas SystemsHexosyltransferasesLipopolysaccharidesMembrane ProteinsNF-kappa BSignal TransductionToll-Like Receptor 4AnimalsCatalytic DomainClustered Regularly Interspaced Short Palindromic RepeatsCryoelectron MicroscopyGlycosylationHEK293 CellsHumansInflammationMicedolichyl-diphosphooligosaccharide - protein glycotransferaseHexosyltransferasesLipopolysaccharidesMembrane ProteinsNF-kappa BSTT3A protein, humanToll-Like Receptor 4CRISPR screeninginhibition mechanismNF-κBN-glycosylationoligosaccharyltransferaseToll-like receptors

Identifiers

PMID38670073
PMCPMC11149550
OpenAlexW4395469468

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.