ArticleProceedings of the National Academy of Sciences of the United States of America2004
Neurofibromatosis 2 (NF2) tumor suppressor merlin inhibits phosphatidylinositol 3-kinase through binding to PIKE-L.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 155 citations in OpenAlex.
- Transient architecture of the embryonic pancreas determines endocrine mass.Research square · 2026Article
- Fimepinostat Promotes Apoptosis and Decreases Cytokine Secretion inInternational journal of molecular sciences · 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
- Interactions among Merlin, Arkadia, and SKOR2 mediate NF2-associated human Schwann cell proliferation.Stem cell research & therapy · 2025Article
- Current molecular understanding of central nervous system schwannomas.Acta neuropathologica communications · 2025Review
- Review
- The molecular biology of NF2/Merlin on tumorigenesis and development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- NF2: An underestimated player in cancer metabolic reprogramming and tumor immunity.NPJ precision oncology · 2024Review
- Meningioma: current updates on genetics, classification, and mouse modeling.Upsala journal of medical sciences · 2024Review
- Review
- High-Throughput Screening of Epigenetic Inhibitors in Meningiomas Identifies HDAC, G9a, and Jumonji-Domain Inhibition as Potential Therapies.Journal of neurological surgery. Part B, Skull base · 2023Article
- Neurofibromatosis type1, type 2, tuberous sclerosis and Von Hippel-Lindau disease.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2023Article
- Hearing loss and vestibular schwannoma: new insights into Schwann cells implication.Cell death & disease · 2023Review
- Genome-wide association analysis identifies a susceptibility locus for sporadic vestibular schwannoma at 9p21.Brain : a journal of neurology · 2023Article
- The genetic landscape and possible therapeutics of neurofibromatosis type 2.Cancer cell international · 2023Review
- Article
- Landscape of genetic variants in sporadic meningiomas captured with clinical genomics.Acta neurochirurgica · 2022Article
- CUDC907, a dual phosphoinositide-3 kinase/histone deacetylase inhibitor, promotes apoptosis of NF2 Schwannoma cells.Oncotarget · 2022Article
- High-Throughput Mechanistic Screening of Epigenetic Compounds for the Potential Treatment of Meningiomas.Journal of clinical medicine · 2021Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Neurofibromatosis 2 (NF2) is a tumor suppressor, although the molecular mechanism accounting for this effect remains unknown. Here, we show that merlin exerts its activity by inhibiting phosphatidylinositol 3-kinase (PI3-kinase), through binding to PIKE-L. Wild-type merlin, but not patient-derived mutant (L64P), binds PIKE-L and inhibits PI3-kinase activity. This suppression of PI3-kinase activity results from merlin disrupting the binding of PIKE-L to PI3-kinase. In addition, merlin suppression of PI3-kinase activity as well as schwannoma cell growth is abrogated by a single PIKE-L point mutation (P187L) that cannot bind merlin but can still activate PI3-kinase. Knocking down PIKE-L with RNA interference abolishes merlin's tumor-suppressive activity. Our data support the hypothesis that PIKE-L is an important mediator of merlin growth suppression.
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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.