Evidence map›Paper›PMID 26748853›Full record

ArticleCurrent biology : CB2016

USP9X Controls EGFR Fate by Deubiquitinating the Endocytic Adaptor Eps15.

Michol Giovanna Savio, Nadine Wollscheid, Elena Cavallaro, Veronica Algisi, Pier Paolo Di Fiore, Sara Sigismund, Elena Maspero, Simona Polo

Erratum issuedOpen access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Current biology : CB, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
3.0field-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

52 citing papers in PubMed, 83 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Michol Giovanna SavioIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy; DIPO, Dipartimento di Oncologia ed Emato-Oncologia, Università degli Studi di Milano, Via di Rudinì 8, 20122 Milan, Italy.
Nadine WollscheidIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy.
Elena CavallaroIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy.
Veronica AlgisiIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy.
Pier Paolo Di FioreIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy; DIPO, Dipartimento di Oncologia ed Emato-Oncologia, Università degli Studi di Milano, Via di Rudinì 8, 20122 Milan, Italy; IEO, Istituto Europeo di Oncologia, Via Ripamonti 435, 20141 Milan, Italy.
Sara SigismundIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy.
Elena MasperoIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy.
Simona PoloIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy; DIPO, Dipartimento di Oncologia ed Emato-Oncologia, Università degli Studi di Milano, Via di Rudinì 8, 20122 Milan, Italy. Electronic address: simona.polo@ifom.eu.
IFOM · ITUniversity of Milan · IT

Funding

Medical Research Council MR/N00941X/1
6 · The paper itself

Abstract

Following activation by its cognate ligand(s), the epidermal growth factor receptor (EGFR) is rapidly routed to the lysosome for degradation in a ubiquitination-dependent fashion. This pathway represents the major mechanism of long-term attenuation of EGFR signaling, and its deregulation is a significant feature in different types of cancers. Here we demonstrate, through a systematic RNAi-based approach, that several deubiquitinating (DUB) enzymes extend or decrease EGFR half-life upon EGF stimulation. We focus on USP9X, whose depletion severely affects EGFR turnover, interfering with its internalization and trafficking. We identify the endocytic protein Eps15 as one of the critical substrates of USP9X, and we map the Eps15 ubiquitination sites. We found that Eps15 monoubiquitination occurs already at minimal dose of EGF stimulation and is essential for EGFR internalization. Overall, our findings identify USP9X as a novel regulator of EGFR endocytosis and suggest a model whereby cycles of ubiquitination and deubiquitination events on endocytic accessory proteins may regulate the internalization and trafficking of the EGFR toward the lysosomes.

Indexed as

Adaptor Proteins, Signal TransducingCell Line, TumorEndocytosisEndosomesEpidermal Growth FactorErbB ReceptorsHumansLysosomesProtein Processing, Post-TranslationalProtein TransportUbiquitin ThiolesteraseAdaptor Proteins, Signal TransducingEGFR protein, humanEpidermal Growth FactorEPS15 protein, humanErbB ReceptorsUbiquitin ThiolesteraseUSP9X protein, humandeubiquitinating enzymesEGFREps15ubiquitinUSP9X

Identifiers

PMID26748853
OpenAlexW2206613509

What OpenQuestion holds

Textmetadata
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.