ArticleeLife2017
Jak2-mediated phosphorylation of Atoh1 is critical for medulloblastoma growth.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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
13 citing papers in PubMed, 20 citations in OpenAlex.
- A single-cell transcriptomic map of the developing Atoh1 lineage identifies neural fate decisions and neuronal diversity in the hindbrain.Developmental cell · 2024Article
- A Network Pharmacology Prediction and Molecular Docking-Based Strategy to Explore the Potential Pharmacological Mechanism ofInternational journal of molecular sciences · 2023Article
- Review
- Cyclin D1 controls development of cerebellar granule cell progenitors through phosphorylation and stabilization of ATOH1.The EMBO journal · 2021Article
- The Role of Neurodevelopmental Pathways in Brain Tumors.Frontiers in cell and developmental biology · 2021Review
- Atonal bHLH transcription factor 1 is an important factor for maintaining the balance of cell proliferation and differentiation in tumorigenesis.Oncology letters · 2020Review
- Doublecortin-like Kinase 1 Regulates α-Synuclein Levels and Toxicity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Medulloblastomics revisited: biological and clinical insights from thousands of patients.Nature reviews. Cancer · 2020Review
- Article
- Molecular profiling predicts meningioma recurrence and reveals loss of DREAM complex repression in aggressive tumors.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- A natural compound derivative P-13 inhibits STAT3 signaling by covalently inhibiting Janus kinase 2.Investigational new drugs · 2019Article
- Principles of tumorigenesis and emerging molecular drivers of SHH-activated medulloblastomas.Annals of clinical and translational neurology · 2019Review
- Raman spectroscopy for medulloblastoma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Treatment for medulloblastoma, the most common malignant brain tumor in children, remains limited to surgical resection, radiation, and traditional chemotherapy; with long-term survival as low as 50-60% for Sonic Hedgehog (Shh)-type medulloblastoma. We have shown that the transcription factor Atonal homologue 1 (Atoh1) is required for Shh-type medulloblastoma development in mice. To determine whether reducing either Atoh1 levels or activity in tumors after their development is beneficial, we studied Atoh1 dosage and modifications in Shh-type medulloblastoma. Heterozygosity of Atoh1 reduced tumor occurrence and prolonged survival. We discovered tyrosine 78 of Atoh1 is phosphorylated by a Jak2-mediated pathway only in tumor-initiating cells and in human SHH-type medulloblastoma. Phosphorylation of tyrosine 78 stabilizes Atoh1, increases Atoh1's transcriptional activity, and is independent of canonical Jak2 signaling. Importantly, inhibition of Jak2 impairs tyrosine 78 phosphorylation and tumor growth in vivo. Taken together, inhibiting Jak2-mediated tyrosine 78 phosphorylation could provide a viable therapy for medulloblastoma.
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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 Socratic graph.