Evidence map›Paper›PMID 27555662›Full record

ArticleScience signaling2016

Negative regulation of NF-κB p65 activity by serine 536 phosphorylation.

Jean-Philippe Pradère, Céline Hernandez, Christiane Koppe, Richard A Friedman, Tom Luedde, Robert F Schwabe

Open access · bronzeAbstract read
In one paragraph

Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

72 citing papers in PubMed, 132 citations in OpenAlex.

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  12. FAM19A5 is an independent prognostic biomarker in thyroid cancer.American journal of translational research · 2026
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12 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 2 countries.

Jean-Philippe PradèreDepartment of Medicine, Columbia University, New York, NY 10032, USA.
Céline HernandezDepartment of Medicine, Columbia University, New York, NY 10032, USA.
Christiane KoppeDepartment of Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany.
Richard A FriedmanBiomedical Informatics Shared Resource, Herbert Irving Comprehensive Cancer Center and Department of Biomedical Informatics, Columbia University, New York, NY 10032, USA.
Tom LueddeDepartment of Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany.
Robert F SchwabeDepartment of Medicine, Columbia University, New York, NY 10032, USA. rfs2102@cumc.columbia.edu.
Columbia University · USRWTH Aachen University · DE

Funding

Targeting Cancer-Associated Myofibroblasts by DNA HypomethylationU54CA163111 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI WANG, TIMOTHY CRAGIN · 2011 to 2015
$2.6M
NCI NIH HHS U54 CA163111
6 · The paper itself

Abstract

Nuclear factor κB (NF-κB) is a master regulator of inflammation and cell death. Whereas most of the activity of NF-κB is regulated through the inhibitor of κB (IκB) kinase (IKK)-dependent degradation of IκB, IKK also phosphorylates subunits of NF-κB. We investigated the contribution of the phosphorylation of the NF-κB subunit p65 at the IKK phosphorylation site serine 536 (Ser(536)) in humans, which is thought to be required for the activation and nuclear translocation of NF-κB. Through experiments with knock-in mice (S534A mice) expressing a mutant p65 with an alanine-to-serine substitution at position 534 (the murine homolog of human Ser(536)), we observed increased expression of NF-κB-dependent genes after injection of mice with the inflammatory stimulus lipopolysaccharide (LPS) or exposure to gamma irradiation, and the enhanced gene expression was most pronounced at late time points. Compared to wild-type mice, S534A mice displayed increased mortality after injection with LPS. Increased NF-κB signaling in the S534A mice was at least in part explained by the increased stability of the S534A p65 protein compared to that of the Ser(534)-phosphorylated wild-type protein. Together, our results suggest that Ser(534) phosphorylation of p65 in mice (and, by extension, Ser(536) phosphorylation of human p65) is not required for its nuclear translocation, but instead inhibits NF-κB signaling to prevent deleterious inflammation.

Indexed as

Signal TransductionAmino Acid SubstitutionAnimalsInflammationLipopolysaccharidesMice, TransgenicMutation, MissensePhosphorylationSerineTranscription Factor RelALipopolysaccharidesRela protein, mouseSerineTranscription Factor RelA

Identifiers

PMID27555662
PMCPMC5327697
OpenAlexW2515697377

What OpenQuestion holds

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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.