ArticleGenes & development2012
A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1.
Article in Genes & development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 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
93 citing papers in PubMed, 167 citations in OpenAlex.
- Circulating Tumor DNA in Neurofibromatosis Type 1: Translating Molecular Discovery into Clinical Surveillance.Diagnostics (Basel, Switzerland) · 2026Review
- NF1 and SPRED1/2 cooperate through RAS-MAPK-independent functions.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The impact of RAS on cell differentiation in health and disease.The Biochemical journal · 2025Review
- The role of SPRED1 mutation in melanoma.European journal of medical research · 2025Review
- Enhancing the sensitivity of lung adenocarcinoma to immune therapeutic agents throughTranslational lung cancer research · 2025Article
- RASopathies and Cardiac Complications: Insights into Mechanisms, Diagnosis, and Innovative Treatments.Current cardiology reviews · 2025Review
- Pigment epithelium derived factor drives melanocyte proliferation and migration in neurofibromatosis café au lait macules.Skin health and disease · 2024Article
- Unraveling neuronal and metabolic alterations in neurofibromatosis type 1.Journal of neurodevelopmental disorders · 2024Review
- The role of CRAF in cancer progression: from molecular mechanisms to precision therapies.Nature reviews. Cancer · 2024Review
- RAS Signaling Gone Awry in the Skin: The Complex Role of RAS in Cutaneous Neurofibroma Pathogenesis, Emerging Biological Insights.The Journal of investigative dermatology · 2023Review
- The oncogenic role of NF1 in gallbladder cancer through regulation of YAP1 stability by direct interaction with YAP1.Journal of translational medicine · 2023Article
- The therapeutic potential of neurofibromin signaling pathways and binding partners.Communications biology · 2023Review
- Destabilizing NF1 variants act in a dominant negative manner through neurofibromin dimerization.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Targeting RAS mutants in malignancies: successes, failures, and reasons for hope.Cancer communications (London, England) · 2023Review
- Functional Assays Combined with Pre-mRNA-Splicing Analysis Improve Variant Classification and Diagnostics for Individuals with Neurofibromatosis Type 1 and Legius Syndrome.Human mutation · 2023Article
- The molecular genetics of RASopathies: An update on novel disease genes and new disorders.American journal of medical genetics. Part C, Seminars in medical genetics · 2022Review
- Mechanistic insights from animal models of neurofibromatosis type 1 cognitive impairment.Disease models & mechanisms · 2022Review
- RAS and beyond: the many faces of the neurofibromatosis type 1 protein.Disease models & mechanisms · 2022Article
- The RASopathies: from pathogenetics to therapeutics.Disease models & mechanisms · 2022Review
- Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The Ras/mitogen-activated protein kinase (MAPK) pathway plays a critical role in transducing mitogenic signals from receptor tyrosine kinases. Loss-of-function mutations in one feedback regulator of Ras/MAPK signaling, SPRED1 (Sprouty-related protein with an EVH1 domain), cause Legius syndrome, an autosomal dominant human disorder that resembles Neurofibromatosis-1 (NF1). Spred1 functions as a negative regulator of the Ras/MAPK pathway; however, the underlying molecular mechanism is poorly understood. Here we show that neurofibromin, the NF1 gene product, is a Spred1-interacting protein that is necessary for Spred1's inhibitory function. We show that Spred1 binding induces the plasma membrane localization of NF1, which subsequently down-regulates Ras-GTP levels. This novel mechanism for the regulation of neurofibromin provides a molecular bridge for understanding the overlapping pathophysiology of NF1 and Legius syndrome.
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.