ArticleEMBO reports2021
USP42 protects ZNRF3/RNF43 from R-spondin-dependent clearance and inhibits Wnt signalling.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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.
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.
Who cites it
33 citing papers in PubMed, 47 citations in OpenAlex.
- Deubiquitinating enzyme USP42 promotes breast cancer progression by inhibiting JNK/p38-mediated apoptosis.Scientific reports · 2025Article
- WNK kinase regulates plasma membrane levels of the WNT inhibitor RNF43: A WNK-RNF43 circuit regulates WNT signal suppression.bioRxiv : the preprint server for biology · 2025Article
- Inhibition of ICAM1 diminishes stemness and enhances antitumor immunity in glioblastoma via β-catenin/PD-L1 signaling.Nature communications · 2025Article
- The interplay between Wnt and mTOR signaling modulates ciliogenesis in human retinal epithelial cells.PLoS biology · 2025Article
- FGF2 Mediated USP42-PPARγ Axis Activation Ameliorates Liver Oxidative Damage and Promotes Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mapping chromatin remodelling in glioblastoma identifies epigenetic regulation of key molecular pathways and novel druggable targets.BMC biology · 2025Article
- Wnt signalosomes: What we know that we do not know.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Targeting USP42 induces DNA damage and inhibits cell growth in prostate cancer.Frontiers in molecular biosciences · 2025Article
- Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025Review
- Gonadal sex reversal at single-cell resolution in Znrf3-deficient mice.Development (Cambridge, England) · 2024Article
- Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress.Nature communications · 2024Article
- New Target(s) for RNF43 Regulation: Implications for Therapeutic Strategies.International journal of molecular sciences · 2024Review
- New insights in ubiquitin-dependent Wnt receptor regulation in tumorigenesis.In vitro cellular & developmental biology. Animal · 2024Review
- Effects ofWorld journal of gastrointestinal oncology · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- [Ubiquitin-specific protease 42 regulates osteogenic differentiation of human adipose-derived stem cells].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2024Article
- Comprehensive analysis of the role of ubiquitin-specific peptidases in colorectal cancer: A systematic review.World journal of gastrointestinal oncology · 2024Article
- The involvement of E3 ubiquitin ligases in the development and progression of colorectal cancer.Cell death discovery · 2023Review
- Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2.Science advances · 2023Article
- The USP46 complex deubiquitylates LRP6 to promote Wnt/β-catenin signaling.Nature communications · 2023Article
Corrections and comments
- Commented on by
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumour suppressors RNF43 and ZNRF3 play a central role in development and tissue homeostasis by promoting the turnover of the Wnt receptors LRP6 and Frizzled (FZD). The stem cell growth factor R-spondin induces auto-ubiquitination and membrane clearance of ZNRF3/RNF43 to promote Wnt signalling. However, the deubiquitinase stabilising ZNRF3/RNF43 at the plasma membrane remains unknown. Here, we show that the USP42 antagonises R-spondin by protecting ZNRF3/RNF43 from ubiquitin-dependent clearance. USP42 binds to the Dishevelled interacting region (DIR) of ZNRF3 and stalls the R-spondin-LGR4-ZNRF3 ternary complex by deubiquitinating ZNRF3. Accordingly, USP42 increases the turnover of LRP6 and Frizzled (FZD) receptors and inhibits Wnt signalling. Furthermore, we show that USP42 functions as a roadblock for paracrine Wnt signalling in colon cancer cells and mouse small intestinal organoids. We provide new mechanistic insights into the regulation R-spondin and conclude that USP42 is crucial for ZNRF3/RNF43 stabilisation at the cell surface.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.