ArticleThe Journal of biological chemistry2011
Inhibition of ubiquitin ligase F-box and WD repeat domain-containing 7α (Fbw7α) causes hepatosteatosis through Krüppel-like factor 5 (KLF5)/peroxisome proliferator-activated receptor γ2 (PPARγ2) pathway but not SREBP-1c protein in mice.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 24 citations in OpenAlex.
- FBXW7 is a multifaceted regulator of the innate immune response to DNA viruses.Cellular & molecular immunology · 2025Article
- Hepatocyte FBXW7-dependent activity of nutrient-sensing nuclear receptors controls systemic energy homeostasis and NASH progression in male mice.Nature communications · 2023Article
- Specificity Proteins (SP) and Krüppel-like Factors (KLF) in Liver Physiology and Pathology.International journal of molecular sciences · 2023Review
- Krüppel-like factor (KLF)5: An emerging foe of cardiovascular health.Journal of molecular and cellular cardiology · 2022Review
- KLF5 Is Induced by FOXO1 and Causes Oxidative Stress and Diabetic Cardiomyopathy.Circulation research · 2021Article
- Ehrlichia chaffeensis TRP120-mediated ubiquitination and proteasomal degradation of tumor suppressor FBW7 increases oncoprotein stability and promotes infection.PLoS pathogens · 2020Article
- Studies of liver tissue identify functional gene regulatory elements associated to gene expression, type 2 diabetes, and other metabolic diseases.Human genomics · 2019Article
- Physiological functions of FBW7 in cancer and metabolism.Cellular signalling · 2018Review
- The transcription factor Klf5 is essential for intrahepatic biliary epithelial tissue remodeling after cholestatic liver injury.The Journal of biological chemistry · 2018Article
- Degradation of the endoplasmic reticulum-anchored transcription factor MyRF by the ubiquitin ligase SCFThe Journal of biological chemistry · 2018Article
- Krüppel-like factors: Crippling and un-crippling metabolic pathways.JACC. Basic to translational science · 2018Article
- SP and KLF Transcription Factors in Digestive Physiology and Diseases.Gastroenterology · 2017Review
- E3 ligase FBXW7 is critical for RIG-I stabilization during antiviral responses.Nature communications · 2017Article
- Article
- Absence of Elovl6 attenuates steatohepatitis but promotes gallstone formation in a lithogenic diet-fed Ldlr(-/-) mouse model.Scientific reports · 2015Article
- Ring finger protein20 regulates hepatic lipid metabolism through protein kinase A-dependent sterol regulatory element binding protein1c degradation.Hepatology (Baltimore, Md.) · 2014Article
- FBW7-mediated ubiquitination and degradation of KLF5.World journal of biological chemistry · 2014Review
- Modes-of-Action Related to Repeated Dose Toxicity: Tissue-Specific Biological Roles of PPAR γ Ligand-Dependent Dysregulation in Nonalcoholic Fatty Liver Disease.PPAR research · 2014Review
- F-box and WD repeat domain-containing-7 (Fbxw7) protein targets endoplasmic reticulum-anchored osteogenic and chondrogenic transcriptional factors for degradation.The Journal of biological chemistry · 2013Article
- Expanding roles for SREBP in metabolism.Cell metabolism · 2012Review
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
F-box and WD repeat domain-containing 7α (Fbw7α) is the substrate recognition component of a ubiquitin ligase that controls the degradation of factors involved in cellular growth, including c-Myc, cyclin E, and c-Jun. In addition, Fbw7α degrades the nuclear form of sterol regulatory element-binding protein (SREBP)-1a, a global regulator of lipid synthesis, particularly during mitosis in cultured cells. This study investigated the in vivo role of Fbw7α in hepatic lipid metabolism. siRNA knockdown of Fbw7α in mice caused marked hepatosteatosis with the accumulation of triglycerides. However, inhibition of Fbw7α did not change the level of nuclear SREBP-1 protein or the expression of genes involved in fatty acid synthesis and oxidation. In vivo experiments on the gain and loss of Fbw7α function indicated that Fbw7α regulated the expression of peroxisome proliferator-activated receptor (PPAR) γ2 and its target genes involved in fatty acid uptake and triglyceride synthesis. These genes included fatty acid transporter Cd36, diacylglycerol acyltransferase 1 (Dgat1), and fat-specific protein 27 (Cidec). The regulation of PPARγ2 by Fbw7α was mediated, at least in part, by the direct degradation of the Krüppel-like factor 5 (KLF5) protein, upstream of PPARγ2 expression. Hepatic Fbw7α contributes to normal fatty acid and triglyceride metabolism, functions that represent novel aspects of this cell growth regulator.
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