Evidence map›Paper›PMID 30926242›Full record

ArticleMolecular cell2019

Distinct USP25 and USP28 Oligomerization States Regulate Deubiquitinating Activity.

Malte Gersch, Jane L Wagstaff, Angela V Toms, Bradford Graves, Stefan M V Freund, David Komander

Open access · hybridAbstract read
In one paragraph

Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

49 citing papers in PubMed, 72 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

6 authors at 4 institutions in 4 countries.

Malte GerschMedical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; Chemical Genomics Centre, Max-Planck-Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany; Department of Chemistry and Chemical Biology, Technical University Dortmund, Otto-Hahn-Str. 4a, 44227 Dortmund, Germany.
Jane L WagstaffMedical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Angela V TomsFORMA Therapeutics, Arsenal Street, Watertown, MA 02472, USA.
Bradford GravesFORMA Therapeutics, Arsenal Street, Watertown, MA 02472, USA.
Stefan M V FreundMedical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
David KomanderMedical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; Ubiquitin Signalling Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3010, Australia. Electronic address: dk@wehi.edu.au.
Forma Therapeutics (United States) · USMRC Laboratory of Molecular Biology · GBMedical Research Council · GBTU Dortmund University · DE

Funding

Medical Research Council MC_U105192732Medical Research Council U105192732
6 · The paper itself

Abstract

The evolutionarily related deubiquitinating enzymes (DUBs) USP25 and USP28 comprise an identical overall domain architecture but are functionally non-redundant: USP28 stabilizes c-MYC and other nuclear proteins, and USP25 regulates inflammatory TRAF signaling. We here compare molecular features of USP25 and USP28. Active enzymes form distinctively shaped dimers, with a dimerizing insertion spatially separating independently active catalytic domains. In USP25, but not USP28, two dimers can form an autoinhibited tetramer, where a USP25-specific, conserved insertion sequence blocks ubiquitin binding. In full-length enzymes, a C-terminal domain with a previously unknown fold has no impact on oligomerization, but N-terminal regions affect the dimer-tetramer equilibrium in vitro. We confirm oligomeric states of USP25 and USP28 in cells and show that modulating oligomerization affects substrate stabilization in accordance with in vitro activity data. Our work highlights how regions outside of the catalytic domain enable a conceptually intriguing interplay of DUB oligomerization and activity.

Indexed as

Protein ConformationAmino Acid SequenceCatalytic DomainDeubiquitinating EnzymesHumansInflammationMutationProtein BindingProtein DomainsProtein MultimerizationProto-Oncogene Proteins c-mybSignal TransductionSubstrate SpecificityTumor Necrosis Factor Receptor-Associated Peptides and ProteinsUbiquitinUbiquitin ThiolesteraseDeubiquitinating EnzymesProto-Oncogene Proteins c-mybTumor Necrosis Factor Receptor-Associated Peptides and ProteinsUbiquitinUbiquitin ThiolesteraseUSP25 protein, humanUSP28 protein, humanc-MYCdeubiquitylating enzymeTRAFubiquitinubiquitin specific protease

Identifiers

PMID30926242
PMCPMC6509359
OpenAlexW2922956498

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.