ArticleDevelopmental cell2011
SAG/RBX2/ROC2 E3 ubiquitin ligase is essential for vascular and neural development by targeting NF1 for degradation.
Article in Developmental cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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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.
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Who cites it
60 citing papers in PubMed, 93 citations in OpenAlex.
- Protein neddylation as a therapeutic target: challenges and opportunities.The Journal of clinical investigation · 2026Review
- RING-Box E3 Ligase Target N-Terminal Lysine 55 to Regulate Turnover of Sp7 Protein.Journal of cellular biochemistry · 2025Article
- A haploinsufficiency restoration strategy corrects neurobehavioral deficits in Nf1+/- mice.The Journal of clinical investigation · 2025Article
- The FBXW7-RPAP2 Axis Controls the Growth of Hepatocellular Carcinoma Cells and Determines the Fate of Liver Cell Differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- E3 Ligase Rbx1 Orchestrates Thymus Development and Fate Determination of αβ-γδ T Cells.Research (Washington, D.C.) · 2025Article
- Ubiquitin Ligase RBX2/SAG Regulates Mitochondrial Ubiquitination and Mitophagy.Circulation research · 2024Article
- Novel insights into the potential applications of stem cells in pulmonary hypertension therapy.Respiratory research · 2024Review
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Review
- The Cullin-RING Ligase Family in Immune Regulation.Advances in experimental medicine and biology · 2024Review
- Targeting neddylation as a novel approach to lung cancer treatment (Review).International journal of oncology · 2023Review
- 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
- The Functional Redundancy of Neddylation E2s and E3s in Modulating the Fitness of Regulatory T Cells.Research (Washington, D.C.) · 2023Article
- The Ube2m-Rbx1 neddylation-Cullin-RING-Ligase proteins are essential for the maintenance of Regulatory T cell fitness.Nature communications · 2022Article
- An integrative pan-cancer analysis revealing the difference in small ring finger family of SCF E3 ubiquitin ligases.Frontiers in immunology · 2022Article
- Tumor Suppressor FBXW7 and Its Regulation of DNA Damage Response and Repair.Frontiers in cell and developmental biology · 2021Review
- The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer.Oncogenesis · 2020Review
- Review
- Transgenic expression of Sag/Rbx2 E3 causes early stage tumor promotion, late stage cytogenesis and acinar loss in the Kras-PDAC model.Neoplasia (New York, N.Y.) · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
SAG/RBX2/ROC2 protein is an essential RING component of SCF E3 ubiquitin ligase. The role of SAG during embryogenesis remains unknown. We report a critical role for SAG in controlling vascular and neural development by modulating RAS activity via promoting degradation of neurofibromatosis type 1 (NF1). Mice mutant for Sag died at embryonic day 11.5-12.5 with severe abnormalities in vascular and nervous system. Sag inactivation caused Nf1 accumulation and Ras inhibition, which blocks embryonic stem (ES) cells from undergoing endothelial differentiation and inhibits angiogenesis and proliferation in teratomas. Simultaneous Nf1 deletion fully rescues the differentiation defects in Sag(-/-) ES cells and partially rescues vascular and neural defects in Sag(-/-) embryos, suggesting that the effects of Sag deletion may not be solely explained by Nf1 misregulation. Collectively, our study identifies NF1 as a physiological substrate of SAG-CUL1-FBXW7 E3 ligase and establishes a ubiquitin-dependent regulatory mechanism for the NF1-RAS pathway during embryogenesis.
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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.