Evidence map›Paper›PMID 30854564›Full record

ArticleNucleic acids research2019

GSK3β-SCFFBXW7α mediated phosphorylation and ubiquitination of IRF1 are required for its transcription-dependent turnover.

Alexander J Garvin, Ahmed H A Khalaf, Alessandro Rettino, Jerome Xicluna, Laura Butler, Joanna R Morris, David M Heery, Nicole M Clarke

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

17 citing papers in PubMed, 30 citations in OpenAlex.

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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

8 authors at 2 institutions in 1 country.

Alexander J GarvinSchool of Pharmacy, University of Nottingham, University Park, Nottingham, UK.
Ahmed H A KhalafSchool of Pharmacy, University of Nottingham, University Park, Nottingham, UK.
Alessandro RettinoSchool of Pharmacy, University of Nottingham, University Park, Nottingham, UK.
Jerome XiclunaSchool of Pharmacy, University of Nottingham, University Park, Nottingham, UK.
Laura ButlerInstitute of Cancer & Genomic Sciences, University of Birmingham, Edgbaston, UK.
Joanna R MorrisInstitute of Cancer & Genomic Sciences, University of Birmingham, Edgbaston, UK.
David M HeerySchool of Pharmacy, University of Nottingham, University Park, Nottingham, UK.
Nicole M ClarkeSchool of Pharmacy, University of Nottingham, University Park, Nottingham, UK.
University of Nottingham · GBUniversity of Birmingham · GB

Funding

Cancer Research UK 11643
6 · The paper itself

Abstract

IRF1 (Interferon Regulatory Factor-1) is the prototype of the IRF family of DNA binding transcription factors. IRF1 protein expression is regulated by transient up-regulation in response to external stimuli followed by rapid degradation via the ubiquitin-proteasome system. Here we report that DNA bound IRF1 turnover is promoted by GSK3β (Glycogen Synthase Kinase 3β) via phosphorylation of the T181 residue which generates a phosphodegron for the SCF (Skp-Cul-Fbox) ubiquitin E3-ligase receptor protein Fbxw7α (F-box/WD40 7). This regulated turnover is essential for IRF1 activity, as mutation of T181 results in an improperly stabilized protein that accumulates at target promoters but fails to induce RNA-Pol-II elongation and subsequent transcription of target genes. Consequently, the anti-proliferative activity of IRF1 is lost in cell lines expressing T181A mutant. Further, cell lines with dysfunctional Fbxw7 are less sensitive to IRF1 overexpression, suggesting an important co-activator function for this ligase complex. As T181 phosphorylation requires both DNA binding and RNA-Pol-II elongation, we propose that this event acts to clear 'spent' molecules of IRF1 from transcriptionally engaged target promoters.

Indexed as

AnimalsCell ProliferationDNA-Binding ProteinsF-Box-WD Repeat-Containing Protein 7Glycogen Synthase Kinase 3 betaHEK293 CellsHumansInterferon Regulatory Factor-1MicePhosphorylationProteasome Endopeptidase ComplexProtein BindingSKP Cullin F-Box Protein LigasesTranscription FactorsUbiquitinationDNA-Binding ProteinsF-Box-WD Repeat-Containing Protein 7Glycogen Synthase Kinase 3 betaInterferon Regulatory Factor-1Irf1 protein, mouseProteasome Endopeptidase ComplexSKP Cullin F-Box Protein LigasesTranscription Factors

Identifiers

PMID30854564
PMCPMC6511875
OpenAlexW2950465204

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.