ArticleMolecular cell2017
NOTCH2 Hajdu-Cheney Mutations Escape SCF
Article in Molecular cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Tumor-derived branched-chain α-keto acids activate Notch signaling in tumor-associated macrophages to limit immunity.Nature immunology · 2026Article
- Myeloid-Specific Deletion ofBiomedicines · 2026Article
- A case of serpentine fibula-polycystic kidney syndrome presenting with foetal limb shortening: a disorder of foetal osteogenesis and part of the phenotypic spectrum of Hajdu-Cheney syndrome.Clinical dysmorphology · 2026Article
- Crosstalk between the circadian clock, intestinal stem cell niche, and epithelial cell fate decision.Genes & diseases · 2025Review
- Targeting Msx2 as a brake in the fusion fate of osteoclasts and an anabolic therapy in pre-clinical models of osteoporosis.Nature communications · 2025Article
- APOE-NOTCH axis governs elastogenesis during human cardiac valve remodeling.Nature cardiovascular research · 2024Article
- Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis.International journal of molecular sciences · 2023Article
- Progress and Current Status in Hajdu-Cheney Syndrome with Focus on Novel Genetic Research.International journal of molecular sciences · 2022Review
- Germline variants in tumor suppressor FBXW7 lead to impaired ubiquitination and a neurodevelopmental syndrome.American journal of human genetics · 2022Article
- Notch signaling pathway: architecture, disease, and therapeutics.Signal transduction and targeted therapy · 2022Review
- Enhancers with cooperative Notch binding sites are more resistant to regulation by the Hairless co-repressor.PLoS genetics · 2021Article
- The FBXW7-NOTCH interactome: A ubiquitin proteasomal system-induced crosstalk modulating oncogenic transformation in human tissues.Cancer reports (Hoboken, N.J.) · 2021Review
- Relevance of Notch Signaling for Bone Metabolism and Regeneration.International journal of molecular sciences · 2021Review
- RNA sequencing analyses reveal differentially expressed genes and pathways as Notch2 targets in B-cell lymphoma.Oncotarget · 2020Article
- Review
- Article
- Ubiquitylomes Analysis of the Whole blood in Postmenopausal Osteoporosis Patients and healthy Postmenopausal Women.Orthopaedic surgery · 2019Article
- The Hajdu Cheney mutation sensitizes mice to the osteolytic actions of tumor necrosis factor α.The Journal of biological chemistry · 2019Article
- Contextual Regulation of Skeletal Physiology by Notch Signaling.Current osteoporosis reports · 2019Review
- Protease-Activated Receptor 1 Deletion Causes Enhanced Osteoclastogenesis in Response to Inflammatory Signals through a Notch2-Dependent Mechanism.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 3 countries.
Funding
Abstract
Hajdu-Cheney syndrome (HCS), a rare autosomal disorder caused by heterozygous mutations in NOTCH2, is clinically characterized by acro-osteolysis, severe osteoporosis, short stature, neurological symptoms, cardiovascular defects, and polycystic kidneys. Recent studies identified that aberrant NOTCH2 signaling and consequent osteoclast hyperactivity are closely associated with the bone-related disorder pathogenesis, but the exact molecular mechanisms remain unclear. Here, we demonstrate that sustained osteoclast activity is largely due to accumulation of NOTCH2 carrying a truncated C terminus that escapes FBW7-mediated ubiquitination and degradation. Mice with osteoclast-specific Fbw7 ablation revealed osteoporotic phenotypes reminiscent of HCS, due to elevated Notch2 signaling. Importantly, administration of Notch inhibitors in Fbw7 conditional knockout mice alleviated progressive bone resorption. These findings highlight the molecular basis of HCS pathogenesis and provide clinical insights into potential targeted therapeutic strategies for skeletal disorders associated with the aberrant FBW7/NOTCH2 pathway as observed in patients with HCS.
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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.