Evidence map›Paper›PMID 31519875›Full record

ArticleNature communications2019

USP7 inhibits Wnt/β-catenin signaling through promoting stabilization of Axin.

Lei Ji, Bo Lu, Raffaella Zamponi, Olga Charlat, Robert Aversa, Zinger Yang, Frederic Sigoillot, Xiaoping Zhu, Tiancen Hu, John S Reece-Hoyes and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

76 citing papers in PubMed, 124 citations in OpenAlex.

  1. Article
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  7. Article
  8. Article
  9. Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025
    Review
  10. Article
  11. Article
  12. The Small Molecule Compound Eupalinolide B Alleviates Neuropathic Pain by Regulating the USP7/Keap1/Nrf2 Pathway.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Article
  13. Research progress of DUB enzyme in breast cancer.Clinical and experimental medicine · 2025
    Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. Review
  20. Article

16 more citing papers are in PubMed but not listed here.

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

15 authors at 3 institutions in 4 countries.

Lei JiNovartis Institutes for Biomedical Research, Novartis Pharma AG, Cambridge, MA, USA.
Bo LuNovartis Institutes for Biomedical Research, Novartis Pharma AG, Cambridge, MA, USA.
Raffaella ZamponiNovartis Institutes for Biomedical Research, Novartis Pharma AG, Cambridge, MA, USA.
Olga CharlatNovartis Institutes for Biomedical Research, Novartis Pharma AG, Cambridge, MA, USA.
Robert AversaNovartis Institutes for Biomedical Research, Novartis Pharma AG, Cambridge, MA, USA.
Zinger YangNovartis Institutes for Biomedical Research, Novartis Pharma AG, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8543-4841
Frederic SigoillotNovartis Institutes for Biomedical Research, Novartis Pharma AG, Cambridge, MA, USA.
Xiaoping ZhuNovartis Institutes for Biomedical Research, Novartis Pharma AG, Cambridge, MA, USA.
Tiancen HuNovartis Institutes for Biomedical Research, Novartis Pharma AG, Cambridge, MA, USA.
John S Reece-HoyesNovartis Institutes for Biomedical Research, Novartis Pharma AG, Cambridge, MA, USA.
Carsten RussNovartis Institutes for Biomedical Research, Novartis Pharma AG, Cambridge, MA, USA.
Gregory MichaudNovartis Institutes for Biomedical Research, Novartis Pharma AG, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3954-4921
Jan S TchorzNovartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
Xiaomo JiangNovartis Institutes for Biomedical Research, Novartis Pharma AG, Cambridge, MA, USA.
Feng CongNovartis Institutes for Biomedical Research, Novartis Pharma AG, Cambridge, MA, USA. feng.cong@novartis.com.
Novartis (United States) · USNovartis (Switzerland) · CHAzienda Sanitaria Unità Locale di Reggio Emilia · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Axin is a key scaffolding protein responsible for the formation of the β-catenin destruction complex. Stability of Axin protein is regulated by the ubiquitin-proteasome system, and modulation of cellular concentration of Axin protein has a profound effect on Wnt/β-catenin signaling. Although E3s promoting Axin ubiquitination have been identified, the deubiquitinase responsible for Axin deubiquitination and stabilization remains unknown. Here, we identify USP7 as a potent negative regulator of Wnt/β-catenin signaling through CRISPR screens. Genetic ablation or pharmacological inhibition of USP7 robustly increases Wnt/β-catenin signaling in multiple cellular systems. USP7 directly interacts with Axin through its TRAF domain, and promotes deubiquitination and stabilization of Axin. Inhibition of USP7 regulates osteoblast differentiation and adipocyte differentiation through increasing Wnt/β-catenin signaling. Our study reveals a critical mechanism that prevents excessive degradation of Axin and identifies USP7 as a target for sensitizing cells to Wnt/β-catenin signaling.

Indexed as

3T3-L1 CellsAdipocytesAnimalsAxin Proteinbeta CateninCell LineCell Line, TumorFlow CytometryHCT116 CellsHumansImmunoprecipitationMiceOsteoblastsProtein StabilityReverse Transcriptase Polymerase Chain ReactionUbiquitinationAxin Proteinbeta CateninUbiquitin-Specific Peptidase 7USP7 protein, humanUsp7 protein, mouse

Identifiers

PMID31519875
PMCPMC6744515
OpenAlexW2972607243

What OpenQuestion holds

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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.