Evidence map›Paper›PMID 35613580›Full record

ArticleCell reports2022

Redox-sensitive E2 Rad6 controls cellular response to oxidative stress via K63-linked ubiquitination of ribosomes.

Vanessa Simões, Blanche K Cizubu, Lana Harley, Ye Zhou, Joshua Pajak, Nathan A Snyder, Jonathan Bouvette, Mario J Borgnia, Gaurav Arya, Alberto Bartesaghi and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2022. 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
3.3field-weighted citation impact, top 7% 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, 39 citations in OpenAlex.

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  14. Paf1 complex subunit Rtf1 stimulates H2B ubiquitylation by interacting with the highly conserved N-terminal helix of Rad6.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
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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

11 authors at 2 institutions in 1 country.

Vanessa SimõesDepartment of Biology, Duke University, Durham, NC 27708, USA.
Blanche K CizubuDepartment of Biology, Duke University, Durham, NC 27708, USA.
Lana HarleyDepartment of Biology, Duke University, Durham, NC 27708, USA.
Ye ZhouDepartment of Computer Science, Department of Biochemistry, and Department of Electrical and Computer Engineering, Duke University, Durham, NC 27708, USA.
Joshua PajakDepartment of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, USA.
Nathan A SnyderDepartment of Biology, Duke University, Durham, NC 27708, USA.
Jonathan BouvetteGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Durham, NC 27709, USA.
Mario J BorgniaGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Durham, NC 27709, USA.
Gaurav AryaDepartment of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, USA.
Alberto BartesaghiDepartment of Computer Science, Department of Biochemistry, and Department of Electrical and Computer Engineering, Duke University, Durham, NC 27708, USA.
Gustavo M SilvaDepartment of Biology, Duke University, Durham, NC 27708, USA. Electronic address: gustavo.silva@duke.edu.
Duke University · USNational Institutes of Health · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5M
NIEHS Cryo-EM Core FacilityZICES103326 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI BORGNIA, MARIO · 2017 to 2025
$17.0M
Dissecting the roles of ubiquitin in translation controlR35GM137954 · NIGMS · DUKE UNIVERSITY · PI Gustavo M Silva · 2020 to 2026
$3.0M
A Computational Platform for In-Situ Structure Determination at Near-Atomic Resolution using Cryo-Electron TomographyR01GM141223 · NIGMS · DUKE UNIVERSITY · PI BARTESAGHI, ALBERTO · 2021 to 2024
$1.5M
Defining the roles of ubiquitination during the environmental stress responseR00ES025835 · NIEHS · DUKE UNIVERSITY · PI SILVA, GUSTAVO M · 2018 to 2020
$905k
Thermo Lumos Tribrid High-Resolution Accurate-Mass Tandem Mass SpectrometerS10OD024999 · OD · DUKE UNIVERSITY · PI MOSELEY, MARTIN ARTHUR · 2018 to 2018
$600k
Defining the roles of ubiquitination during the environmental stress responseK99ES025835 · NIEHS · NEW YORK UNIVERSITY · PI SILVA, GUSTAVO M · 2015 to 2016
$205k
Intramural NIH HHS ZIC ES103326NCI NIH HHS P30 CA016086NIEHS NIH HHS K99 ES025835NIEHS NIH HHS R00 ES025835NIGMS NIH HHS R01 GM141223NIGMS NIH HHS R35 GM137954
6 · The paper itself

Abstract

Protein ubiquitination is an essential process that rapidly regulates protein synthesis, function, and fate in dynamic environments. Within its non-proteolytic functions, we showed that K63-linked polyubiquitinated conjugates heavily accumulate in yeast cells exposed to oxidative stress, stalling ribosomes at elongation. K63-ubiquitinated conjugates accumulate mostly because of redox inhibition of the deubiquitinating enzyme Ubp2; however, the role and regulation of ubiquitin-conjugating enzymes (E2) in this pathway remained unclear. Here, we show that the E2 Rad6 associates and modifies ribosomes during stress. We further demonstrate that Rad6 and its human homolog UBE2A are redox regulated by forming a reversible disulfide with the E1 ubiquitin-activating enzyme (Uba1). This redox regulation is part of a negative feedback regulation, which controls the levels of K63 ubiquitination under stress. Finally, we show that Rad6 activity is necessary to regulate translation, antioxidant defense, and adaptation to stress, thus providing an additional physiological role for this multifunctional enzyme.

Indexed as

RibosomesUbiquitin-Conjugating EnzymesHumansOxidation-ReductionOxidative StressUbiquitin-Activating EnzymesUbiquitinationUBE2A protein, humanUbiquitin-Activating EnzymesUbiquitin-Conjugating EnzymesCP: Molecular biologyK63-linked ubiquitinationoxidative stressRad6ribosome ubiquitinationstress responsetranslation

Identifiers

PMID35613580
PMCPMC9215706
OpenAlexW4281387142

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.