Evidence map›Paper›PMID 35770973›Full record

ArticleeLife2022

Adaptor linked K63 di-ubiquitin activates Nedd4/Rsp5 E3 ligase.

Lu Zhu, Qing Zhang, Ciro D Cordeiro, Sudeep Banjade, Richa Sardana, Yuxin Mao, Scott D Emr

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 31% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Bacterial mimicry of eukaryotic HECT ubiquitin ligation.bioRxiv : the preprint server for biology · 2023
    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

7 authors at 1 institution in 1 country.

Lu ZhuWeill Institute of Cell and Molecular Biology, Cornell University, Ithaca, United States.ORCID 0000-0001-9438-9296
Qing ZhangWeill Institute of Cell and Molecular Biology, Cornell University, Ithaca, United States.
Ciro D CordeiroWeill Institute of Cell and Molecular Biology, Cornell University, Ithaca, United States.
Sudeep BanjadeWeill Institute of Cell and Molecular Biology, Cornell University, Ithaca, United States.ORCID 0000-0002-5920-891X
Richa SardanaWeill Institute of Cell and Molecular Biology, Cornell University, Ithaca, United States.
Yuxin MaoWeill Institute of Cell and Molecular Biology, Cornell University, Ithaca, United States.ORCID 0000-0002-5064-1397
Scott D EmrWeill Institute of Cell and Molecular Biology, Cornell University, Ithaca, United States.ORCID 0000-0002-5408-6781
Cornell University · US

Funding

Di-ubiquitin modification of ubiquitin ligase adaptors in membrane protein downregulationR01GM144452 · NIGMS · CORNELL UNIVERSITY · PI EMR, SCOTT D, MAO, YUXIN · 2022 to 2025
$1.6M
NIGMS NIH HHS R01 GM144452
6 · The paper itself

Abstract

Nedd4/Rsp5 family E3 ligases mediate numerous cellular processes, many of which require the E3 ligase to interact with PY motif containing adaptor proteins. Several arrestin-related trafficking adaptors (ARTs) of Rsp5 were self-ubiquitinated for activation, but the regulation mechanism remains elusive. Remarkably, we demonstrate that Art1, Art4, and Art5 undergo K63-linked di-ubiquitination by Rsp5. This modification enhances the plasma membrane recruitment of Rsp5 by Art1 or Art5 upon substrate induction, required for cargo protein ubiquitination. In agreement with these observations, we find that di-ubiquitin strengthens the interaction between the pombe orthologs of Rsp5 and Art1, Pub1, and Any1. Furthermore, we discover that the homologous to E6AP C-terminus (HECT) domain exosite protects the K63-linked di-ubiquitin on the adaptors from cleavage by the deubiquitination enzyme Ubp2. Together, our study uncovers a novel ubiquitination modification implemented by Rsp5 adaptor proteins, underscoring the regulatory mechanism of how adaptor proteins control the recruitment, and activity of Rsp5 for the turnover of membrane proteins.

Indexed as

Saccharomyces cerevisiae ProteinsUbiquitinAdaptor Proteins, Signal TransducingEndosomal Sorting Complexes Required for TransportNedd4 Ubiquitin Protein LigasesPoly(A)-Binding ProteinsSaccharomyces cerevisiaeUbiquitinationUbiquitin-Protein Ligase ComplexesUbiquitin-Protein LigasesAdaptor Proteins, Signal TransducingEndosomal Sorting Complexes Required for TransportNedd4 Ubiquitin Protein LigasesPoly(A)-Binding ProteinsPUB1 protein, S cerevisiaeRSP5 protein, S cerevisiaeSaccharomyces cerevisiae ProteinsUbiquitinUbiquitin-Protein Ligase ComplexesUbiquitin-Protein Ligasesadaptorcell biologyE3 ligaseK63 di-ubiquitinNedd4/Rsp5S. cerevisiaeubiquitination

Identifiers

PMID35770973
PMCPMC9282857
OpenAlexW4283718498

What Socratic 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 Socratic graph.