ArticleCell2010
Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus.
Article in Cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 211 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
211 citing papers in PubMed, 2 syntheses or guidelines pooled it, 321 citations in OpenAlex.
- Current Understanding of Hearing Loss in Sporadic Vestibular Schwannomas: A Systematic Review.Frontiers in oncology · 2021Pooled it
- Contemporary Molecular Biology of Sporadic Vestibular Schwannomas: A Systematic Review and Clinical Implications.The journal of international advanced otology · 2018Pooled it
- Context matters in PROTAC design: navigating the trade-off between degradation and developability.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Structural basis of diverse substrate recruitment by the HIV-1 Vpr-hijacked CRL4(VprBP) E3 ligase.PLoS pathogens · 2026Article
- Targeting lysine-specific demethylase 1 inhibits melanoma metastasis via the NF2-Hippo-YAP pathway.Cell death & disease · 2026Article
- Emerging systemic treatment strategies for vestibular schwannoma.Journal of neuro-oncology · 2026Review
- T-cell-targeted immunotherapy in neurofibromatosis type 2-related vestibular schwannoma: current evidence and future direction.Brain communications · 2026Review
- Variable Schwann cell merlin inactivation is targetable with TEAD1 inhibition in schwannomas.bioRxiv : the preprint server for biology · 2025Article
- Review
- OICR-41103 as a chemical probe for the DCAF1 WD40 domain.Communications biology · 2025Article
- Interactions among Merlin, Arkadia, and SKOR2 mediate NF2-associated human Schwann cell proliferation.Stem cell research & therapy · 2025Article
- Malignant Meningiomas: From Diagnostics to Treatment.Diagnostics (Basel, Switzerland) · 2025Review
- Current molecular understanding of central nervous system schwannomas.Acta neuropathologica communications · 2025Review
- Somatic copy number deletion of chromosome 22q in papillary thyroid carcinoma.European thyroid journal · 2025Article
- WWC proteins-mediated compensatory mechanism restricts schwannomatosis driven byScience advances · 2025Article
- Context-specific targeting of focal adhesion kinase in brain tumors: lessons from glioblastoma and neurofibromatosis type 2-mutant meningioma.Frontiers in oncology · 2025Review
- Functional annotation of the Hippo pathway somatic mutations in human cancers.Nature communications · 2024Article
- Meningioma: International Consortium on Meningiomas consensus review on scientific advances and treatment paradigms for clinicians, researchers, and patients.Neuro-oncology · 2024Review
- NF2: An underestimated player in cancer metabolic reprogramming and tumor immunity.NPJ precision oncology · 2024Review
- NF2-Related Schwannomatosis (NF2): Molecular Insights and Therapeutic Avenues.International journal of molecular sciences · 2024Review
151 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Current models imply that the FERM domain protein Merlin, encoded by the tumor suppressor NF2, inhibits mitogenic signaling at or near the plasma membrane. Here, we show that the closed, growth-inhibitory form of Merlin accumulates in the nucleus, binds to the E3 ubiquitin ligase CRL4(DCAF1), and suppresses its activity. Depletion of DCAF1 blocks the promitogenic effect of inactivation of Merlin. Conversely, enforced expression of a Merlin-insensitive mutant of DCAF1 counteracts the antimitogenic effect of Merlin. Re-expression of Merlin and silencing of DCAF1 implement a similar, tumor-suppressive program of gene expression. Tumor-derived mutations invariably disrupt Merlin's ability to interact with or inhibit CRL4(DCAF1). Finally, depletion of DCAF1 inhibits the hyperproliferation of Schwannoma cells from NF2 patients and suppresses the oncogenic potential of Merlin-deficient tumor cell lines. We propose that Merlin suppresses tumorigenesis by translocating to the nucleus to inhibit CRL4(DCAF1).
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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.