Evidence map›Paper›PMID 34927784›Full record

ArticleEMBO reports2022

ENTREP/FAM189A2 encodes a new ITCH ubiquitin ligase activator that is downregulated in breast cancer.

Takumi Tsunoda, Miho Riku, Norika Yamada, Hikaru Tsuchiya, Takuya Tomita, Minako Suzuki, Mari Kizuki, Akihito Inoko, Hideaki Ito, Kenta Murotani and 3 more

Open access · hybridAbstract read
In one paragraph

Article in EMBO reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

12 citing papers in PubMed, 19 citations in OpenAlex.

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  9. Genenames.org: the HGNC resources in 2023.Nucleic acids research · 2023
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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

13 authors at 3 institutions in 1 country.

Takumi TsunodaDepartment of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan.
Miho RikuDepartment of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan.
Norika YamadaDepartment of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan.
Hikaru TsuchiyaProtein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Takuya TomitaProtein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.ORCID 0000-0003-4568-9940
Minako SuzukiDepartment of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan.
Mari KizukiDepartment of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan.
Akihito InokoDepartment of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan.ORCID 0000-0002-6739-2948
Hideaki ItoDepartment of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan.
Kenta MurotaniBiostatistics Center, Kurume University, Kurume, Japan.
Hideki MurakamiDepartment of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan.
Yasushi SaekiProtein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.ORCID 0000-0002-9202-5453
Kenji KasaiDepartment of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan.ORCID 0000-0001-6566-9483
Aichi Medical University · JPTokyo Metropolitan Institute of Medical Science · JPKurume University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The HECT-type ubiquitin E3 ligases including ITCH regulate many aspects of cellular function through ubiquitinating various substrates. These ligases are known to be allosterically autoinhibited and to require an activator protein to fully achieve the ubiquitination of their substrates. Here we demonstrate that FAM189A2, a downregulated gene in breast cancer, encodes a new type of ITCH activator. FAM189A2 is a transmembrane protein harboring PPxY motifs, and the motifs mediate its association with and ubiquitination by ITCH. FAM189A2 also associates with Epsin and accumulates in early and late endosomes along with ITCH. Intriguingly, FAM189A2 facilitates the association of a chemokine receptor CXCR4 with ITCH and enhances ITCH-mediated ubiquitination of CXCR4. FAM189A2-knockout prohibits CXCL12-induced endocytosis of CXCR4, thereby enhancing the effects of CXCL12 on the chemotaxis and mammosphere formation of breast cancer cells. In comparison to other activators or adaptors known in the previous studies, FAM189A2 is a unique activator for ITCH to desensitize CXCR4 activity, and we here propose that FAM189A2 be renamed as ENdosomal TRansmembrane binding with EPsin (ENTREP).

Indexed as

Breast NeoplasmsRepressor ProteinsUbiquitin-Protein LigasesChemokine CXCL12FemaleGene Knockout TechniquesHumansReceptors, CXCR4UbiquitinationChemokine CXCL12CXCL12 protein, humanCXCR4 protein, humanITCH protein, humanReceptors, CXCR4Repressor ProteinsUbiquitin-Protein Ligasesbreast cancerCXCR4ENTREPFAM189A2ITCH

Identifiers

PMID34927784
PMCPMC8811627
OpenAlexW4200374630

What OpenQuestion holds

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Registered trials

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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.