Evidence map›Paper›PMID 31636182›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2019

Repression of eEF2K transcription by NF-κB tunes translation elongation to inflammation and dsDNA-sensing.

Christopher Bianco, Letitia Thompson, Ian Mohr

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

16 citing papers in PubMed, 40 citations in OpenAlex.

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  16. Disease Activity-Associated Alteration of mRNA mFrontiers in cell and developmental biology · 2020
    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

3 authors at 1 institution in 1 country.

Christopher BiancoDepartment of Microbiology, NYU School of Medicine, New York, NY 10016.
Letitia ThompsonDepartment of Microbiology, NYU School of Medicine, New York, NY 10016.
Ian MohrDepartment of Microbiology, NYU School of Medicine, New York, NY 10016; ian.mohr@med.nyu.edu.
New York University · US

Funding

TRAINING PROGRAM: MECHANISMS OF VIRUS-HOST INTERACTIONST32AI007647 · NIAID · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI Domenico Tortorella · 2000 to 2026
$11.5M
INFECTIOUS DISEASES &BASIC MICROBIOLOGICAL MECHANISMST32AI007180 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI WEISER, JEFFREY NEAL · 1985 to 2022
$8.9M
Control of Translation in Herpesvirus Infected Cells - Resubmission - 1R01GM056927 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Ian J Mohr · 1999 to 2026
$7.6M
Virus Host Interactions that Regulate Translation in Cells Infected with HSV-1R01AI073898 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MOHR, IAN J · 2008 to 2020
$5.0M
NIAID NIH HHS R01 AI073898NIAID NIH HHS T32 AI007180NIAID NIH HHS T32 AI007647NIGMS NIH HHS R01 GM056927
6 · The paper itself

Abstract

Gene expression is rapidly remodeled by infection and inflammation in part via transcription factor NF-κB activation and regulated protein synthesis. While protein synthesis is largely controlled by mRNA translation initiation, whether cellular translation elongation factors are responsive to inflammation and infection remains poorly understood. Here, we reveal a surprising mechanism whereby NF-κB restricts phosphorylation of the critical translation elongation factor eEF2, which catalyzes the protein synthesis translocation step. Upon exposure to NF-κB-activating stimuli, including TNFα, human cytomegalovirus infection, or double-stranded DNA, eEF2 phosphorylation on Thr56, which slows elongation to limit protein synthesis, and the overall abundance of eEF2 kinase (eEF2K) are reduced. Significantly, this reflected a p65 NF-κB subunit-dependent reduction in eEF2K pre-mRNA, indicating that NF-κB activation represses eEF2K transcription to decrease eEF2K protein levels. Finally, we demonstrate that reducing eEF2K abundance regulates protein synthesis in response to a bacterial toxin that inactivates eEF2. This establishes that NF-κB activation by diverse physiological effectors controls eEF2 activity via a transcriptional repression mechanism that reduces eEF2K polypeptide abundance to preclude eEF2 phosphorylation, thereby stimulating translation elongation and protein synthesis. Moreover, it illustrates how nuclear transcription regulation shapes translation elongation factor activity and exposes how eEF2 is integrated into innate immune response networks orchestrated by NF-κB.

Indexed as

Protein BiosynthesisAmino Acid MotifsDNAElongation Factor 2 KinaseHumansInflammationNF-kappa BPeptide Elongation Factor 2PhosphorylationTranscription Factor RelADNAEEF2K protein, humanElongation Factor 2 KinaseNF-kappa BPeptide Elongation Factor 2Transcription Factor RelAdouble-strand DNA-sensingeEF2 and eEF2KHCMV infectionNF-κB activationtranslation elongation

Identifiers

PMID31636182
PMCPMC6842605
OpenAlexW2981628170

What OpenQuestion holds

Textmetadata
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.