Evidence map›Paper›PMID 33156996›Full record

ArticleMolecular cell2020

Proteasome-Bound UCH37/UCHL5 Debranches Ubiquitin Chains to Promote Degradation.

Kirandeep K Deol, Sean O Crowe, Jiale Du, Heather A Bisbee, Robert G Guenette, Eric R Strieter

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

55 citing papers in PubMed, 90 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 2 institutions in 1 country.

Kirandeep K DeolDepartment of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USA.
Sean O CroweDepartment of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USA; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Jiale DuDepartment of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USA.
Heather A BisbeeMolecular & Cellular Biology Graduate Program, University of Massachusetts Amherst, Amherst, MA 01003, USA.
Robert G GuenetteDepartment of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USA; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Eric R StrieterDepartment of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USA; Molecular & Cellular Biology Graduate Program, University of Massachusetts Amherst, Amherst, MA 01003, USA. Electronic address: estrieter@umass.edu.
University of Massachusetts Amherst · USUniversity of Wisconsin–Madison · US

Funding

BIOTECHNOLOGY TRAINING PROGRAMT32GM008349 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI FOX, BRIAN G · 1989 to 2019
$22.5M
CHEMISTRY-BIOLOGY INTERFACE PREDOCTORAL TRAINING GRANTST32GM008515 · NIGMS · UNIVERSITY OF MASSACHUSETTS AMHERST · PI THOMPSON, LYNMARIE K. · 1995 to 2020
$4.3M
Understanding the Function of Deubiquitinases Using Chemical Tools: Administrative SupplementR01GM110543 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI STRIETER, ERIC ROBERT · 2014 to 2022
$2.9M
Acquisition of an Orbitrap MSS10OD010645 · OD · UNIVERSITY OF MASSACHUSETTS AMHERST · PI EYLES, STEPHEN J. · 2013 to 2013
$600k
NIGMS NIH HHS R01 GM110543NIGMS NIH HHS T32 GM008349NIGMS NIH HHS T32 GM008515NIH HHS S10 OD010645
6 · The paper itself

Abstract

The linkage, length, and architecture of ubiquitin (Ub) chains are all important variables in providing tight control over many biological paradigms. There are clear roles for branched architectures in regulating proteasome-mediated degradation, but the proteins that selectively recognize and process these atypical chains are unknown. Here, using synthetic and enzyme-derived ubiquitin chains along with intact mass spectrometry, we report that UCH37/UCHL5, a proteasome-associated deubiquitinase, cleaves K48 branched chains. The activity and selectivity toward branched chains is markedly enhanced by the proteasomal Ub receptor RPN13/ADRM1. Using reconstituted proteasome complexes, we find that chain debranching promotes degradation of substrates modified with branched chains under multi-turnover conditions. These results are further supported by proteome-wide pulse-chase experiments, which show that the loss of UCH37 activity impairs global protein turnover. Our work therefore defines UCH37 as a debranching deubiquitinase important for promoting proteasomal degradation.

Indexed as

ProteolysisHEK293 CellsHumansIntracellular Signaling Peptides and ProteinsProteasome Endopeptidase ComplexUbiquitinUbiquitin ThiolesteraseADRM1 protein, humanIntracellular Signaling Peptides and ProteinsProteasome Endopeptidase ComplexUbiquitinUbiquitin ThiolesteraseUCHL5 protein, humanbranched ubiquitin chainsdeubiquitinaseproteasomeubiquitinUCH37UCHL5

Identifiers

PMID33156996
PMCPMC7718437
OpenAlexW3096525038

What OpenQuestion holds

Textmetadata
LicenceTDM
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.