ArticleCell research2013
FBW7 regulates endothelial functions by targeting KLF2 for ubiquitination and degradation.
Article in Cell research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 66 citations in OpenAlex.
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- Post-translational modification gene signatures implicate FBXW7 in immune and vascular dysregulation of Moyamoya disease.Frontiers in genetics · 2025Article
- Targeting the E2F1/Rb/HDAC1 axis with the small molecule HR488B effectively inhibits colorectal cancer growth.Cell death & disease · 2023Article
- Activation of autophagy triggers mitochondrial loss and changes acetylation profile relevant for mechanotransduction in bladder cancer cells.Archives of toxicology · 2023Article
- Notch activation suppresses endothelial cell migration and sprouting via miR-223-3p targeting Fbxw7.In vitro cellular & developmental biology. Animal · 2022Article
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- HIF-1α in Osteoarthritis: From Pathogenesis to Therapeutic Implications.Frontiers in pharmacology · 2022Review
- An ERK5-KLF2 signalling module regulates early embryonic gene expression and telomere rejuvenation in stem cells.The Biochemical journal · 2021Article
- Tumor Suppressor FBXW7 and Its Regulation of DNA Damage Response and Repair.Frontiers in cell and developmental biology · 2021Review
- FGFC1 Selectively Inhibits Erlotinib-Resistant Non-Small Cell Lung CancerFrontiers in pharmacology · 2021Article
- Myeloid FBW7 deficiency disrupts redox homeostasis and aggravates dietary-induced insulin resistance.Redox biology · 2020Article
- FBXW7 in Cancer: What Has Been Unraveled Thus Far?Cancers · 2019Review
- Molecular characterization of sessile serrated adenoma/polyps with dysplasia/carcinoma based on immunohistochemistry, next-generation sequencing, and microsatellite instability testing: a case series study.Diagnostic pathology · 2018Article
- SCFNature communications · 2018Article
- Pseudopodium-enriched atypical kinase 1 mediates angiogenesis by modulating GATA2-dependent VEGFR2 transcription.Cell discovery · 2018Article
- KLF2 in Regulation of NF-κB-Mediated Immune Cell Function and Inflammation.International journal of molecular sciences · 2017Review
- CK1δ/GSK3β/FBXW7α axis promotes degradation of the ZNF322A oncoprotein to suppress lung cancer progression.Oncogene · 2017Article
- FBXW7 missense mutation: a novel negative prognostic factor in metastatic colorectal adenocarcinoma.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
F-box and WD repeat domain-containing 7 (FBW7), the substrate-binding subunit of E3 ubiquitin ligase SCF(FBW7) (a complex of SKP1, cullin-1 and FBW7), plays important roles in various physiological and pathological processes. Although FBW7 is required for vascular development, its function in the endothelium remains to be investigated. In this study, we show that FBW7 is an important regulator of endothelial functions, including angiogenesis, leukocyte adhesion and the endothelial barrier integrity. Using RNA interference, we found that the depletion of FBW7 markedly impairs angiogenesis in vitro and in vivo. We identified the zinc finger transcription factor Krüppel-like factor 2 (KLF2) as a physiological target of FBW7 in endothelial cells. Knockdown of FBW7 expression resulted in the accumulation of endogenous KLF2 protein in endothelial cells. FBW7-mediated KLF2 destruction was shown to depend on the phosphorylation of KLF2 via glycogen synthase kinase-3 (GSK3) at two conserved phosphodegrons. Mutating these phosphodegron motifs abolished the FBW7-mediated degradation and ubiquitination of KLF2. The siRNA-mediated knockdown of FBW7 showed that KLF2 is an essential target of FBW7 in the regulation of endothelial functions. Moreover, FBW7-mediated KLF2 degradation was shown to be critical for angiogenesis in teratomas and in zebrafish development. Taken together, our study suggests a role for FBW7 in the processes of endothelial cell migration, angiogenesis, inflammation and barrier integrity, and provides novel insights into the regulation of KLF2 stability in vivo.
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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.