Evidence map›Paper›PMID 36961408›Full record

ArticleeLife2023

HUWE1 controls tristetraprolin proteasomal degradation by regulating its phosphorylation.

Sara Scinicariello, Adrian Soderholm, Markus Schäfer, Alexandra Shulkina, Irene Schwartz, Kathrin Hacker, Rebeca Gogova, Robert Kalis, Kimon Froussios, Valentina Budroni and 5 more

Open access · goldFull text read
In one paragraph

Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

11 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
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  10. Macrophage variants in laboratory research: most are well done, but some are RAW.Frontiers in cellular and infection microbiology · 2024
    Review
  11. 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 2 institutions in 1 country.

Sara ScinicarielloDepartment of Microbiology, Immunobiology and Genetics, Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC), Vienna, Austria.
Adrian SoderholmDepartment of Microbiology, Immunobiology and Genetics, Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC), Vienna, Austria.
Markus SchäferResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.
Alexandra ShulkinaDepartment of Microbiology, Immunobiology and Genetics, Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC), Vienna, Austria.
Irene SchwartzDepartment of Microbiology, Immunobiology and Genetics, Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC), Vienna, Austria.
Kathrin HackerDepartment of Microbiology, Immunobiology and Genetics, Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC), Vienna, Austria.
Rebeca GogovaVienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, Vienna BioCenter (VBC), Vienna, Austria.
Robert KalisVienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, Vienna BioCenter (VBC), Vienna, Austria.ORCID 0000-0001-7553-4806
Kimon FroussiosResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.ORCID 0000-0003-2812-0525
Valentina BudroniDepartment of Microbiology, Immunobiology and Genetics, Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC), Vienna, Austria.
Annika BestehornDepartment of Microbiology, Immunobiology and Genetics, Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC), Vienna, Austria.
Tim ClausenResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.ORCID 0000-0003-1582-6924
Pavel KovarikDepartment of Microbiology, Immunobiology and Genetics, Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC), Vienna, Austria.
Johannes ZuberResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.ORCID 0000-0001-8810-6835
Gijs A VersteegDepartment of Microbiology, Immunobiology and Genetics, Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC), Vienna, Austria.ORCID 0000-0002-6150-2165
University of Vienna · ATResearch Institute of Molecular Pathology · AT

Funding

Austrian Science Fund FWF P 30415Austrian Science Fund FWF P 31848Austrian Science Fund FWF P 33000Austrian Science Fund FWF W 1261
6 · The paper itself

Abstract

Tristetraprolin (TTP) is a critical negative immune regulator. It binds AU-rich elements in the untranslated-regions of many mRNAs encoding pro-inflammatory mediators, thereby accelerating their decay. A key but poorly understood mechanism of TTP regulation is its timely proteolytic removal: TTP is degraded by the proteasome through yet unidentified phosphorylation-controlled drivers. In this study, we set out to identify factors controlling TTP stability. Cellular assays showed that TTP is strongly lysine-ubiquitinated, which is required for its turnover. A genetic screen identified the ubiquitin E3 ligase HUWE1 as a strong regulator of TTP proteasomal degradation, which we found to control TTP stability indirectly by regulating its phosphorylation. Pharmacological assessment of multiple kinases revealed that HUWE1-regulated TTP phosphorylation and stability was independent of the previously characterized effects of MAPK-mediated S52/S178 phosphorylation. HUWE1 function was dependent on phosphatase and E3 ligase binding sites identified in the TTP C-terminus. Our findings indicate that while phosphorylation of S52/S178 is critical for TTP stabilization at earlier times after pro-inflammatory stimulation, phosphorylation of the TTP C-terminus controls its stability at later stages.

Indexed as

TristetraprolinUbiquitin-Protein LigasesPhosphorylationProteolysisRNA StabilityUbiquitinTristetraprolinUbiquitinUbiquitin-Protein Ligasescell biologye3 ligasehumanhuwe1immunologyinflammationmousetristetraprolinubiquitin

Identifiers

PMID36961408
PMCPMC10038661
OpenAlexW4360807738

What OpenQuestion holds

Textfull text, public
LicenceCC BY
measurements read150
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.