Evidence map›Paper›PMID 31956026›Full record

ArticleCurrent biology : CB2020

A Cycle of Ubiquitination Regulates Adaptor Function of the Nedd4-Family Ubiquitin Ligase Rsp5.

Chris MacDonald, S Brookhart Shields, Charlotte A Williams, Stanley Winistorfer, Robert C Piper

Open access · bronzeAbstract read
In one paragraph

Article in Current biology : CB, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

22 citing papers in PubMed, 41 citations in OpenAlex.

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  7. Bro1 family proteins harmonize cargo sorting with vesicle formation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022
    Article
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  11. α-Arrestins and Their Functions: From Yeast to Human Health.International journal of molecular sciences · 2022
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Adaptors as the regulators of HECT ubiquitin ligases.Cell death and differentiation · 2021
    Review
  19. Article
  20. Induction and Repression of Hydrolase Genes inFrontiers in microbiology · 2021
    Review
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

5 authors at 1 institution in 1 country.

Chris MacDonaldDepartment of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA.
S Brookhart ShieldsDepartment of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA.
Charlotte A WilliamsDepartment of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA.
Stanley WinistorferDepartment of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA.
Robert C PiperDepartment of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA. Electronic address: robert-piper@uiowa.edu.
University of Iowa · US

Funding

Ubiquitin-Dependent Sorting in Endosomes and the TGNR01GM058202 · NIGMS · UNIVERSITY OF IOWA · PI PIPER, ROBERT C · 1998 to 2025
$8.9M
Training Program in Hypertension, Kidney Disease & Cell BiologyT32DK007690 · NIDDK · UNIVERSITY OF IOWA · PI HUANG, CHOU-LONG, RAHMOUNI, KAMAL · 1992 to 2022
$2.8M
NIDDK NIH HHS T32 DK007690NIGMS NIH HHS R01 GM058202Wellcome Trust 204636/Z/16/Z
6 · The paper itself

Abstract

In yeast, the main ubiquitin ligase responsible for the sorting of proteins to the lysosomal vacuole is Rsp5, a member of the Nedd4 family of ligases whose distinguishing features are a catalytic homologous to E6AP C terminus (HECT) domain and 3 central WW domains that bind PY motifs in target proteins. Many substrates do not bind Rsp5 directly and instead rely on PY-containing adaptor proteins that interact with Rsp5. Recent studies indicate that the activities of these adaptors are elevated when they undergo ubiquitination, yet the mechanism whereby ubiquitination activates the adaptors and how this process is regulated remain unclear. Here, we report on a mechanism that explains how ubiquitination stimulates adaptor function and how this process can be regulated by the Rsp5-associated deubiquitinase, Ubp2. Our overexpression experiments revealed that several adaptors compete for Rsp5 in vivo. We found that the ability of the adaptors to compete effectively was enhanced by their ubiquitination and diminished by a block of their ubiquitination. Ubiquitination-dependent adaptor activation required a ubiquitin-binding surface within the Rsp5 catalytic HECT domain. Finally, like constitutively ubiquitinated adaptors, a Ubp2 deficiency increased both the adaptor activity and the ability to compete for Rsp5. Our data support a model whereby ubiquitinated Rsp5 adaptors are more active when "locked" onto Rsp5 via its N-lobe ubiquitin-binding surface and less active when they are "unlocked" by Ubp2-mediated deubiquitination.

Indexed as

Gene Expression Regulation, FungalUbiquitinationEndopeptidasesEndosomal Sorting Complexes Required for TransportMicroorganisms, Genetically-ModifiedSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsUbiquitin-Protein Ligase ComplexesEndopeptidasesEndosomal Sorting Complexes Required for TransportRSP5 protein, S cerevisiaeSaccharomyces cerevisiae Proteinsubiquitin-Nalpha-protein hydrolaseUbiquitin-Protein Ligase ComplexesE3-ligaseendosomelysosomeubiquitin

Identifiers

PMID31956026
PMCPMC7197006
OpenAlexW2999559586

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.