ArticleThe Journal of biological chemistry2010
The Fbw7/human CDC4 tumor suppressor targets proproliferative factor KLF5 for ubiquitination and degradation through multiple phosphodegron motifs.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 113 citations in OpenAlex.
- FBXW7 mutations reprogram glucose metabolism by activating the ETV6-GLUT1 axis.Molecular cancer · 2026Article
- A novel peptide 66CTG stabilizes Myc proto-oncogene protein to promote triple-negative breast cancer growth.Signal transduction and targeted therapy · 2025Article
- Inhibition of KLF5 promotes ferroptosis via the ZEB1/HMOX1 axis to enhance sensitivity to oxaliplatin in cancer cells.Cell death & disease · 2025Article
- Abrogation of KLF5 sensitizesActa biochimica et biophysica Sinica · 2024Article
- TRAF4-Mediated LAMTOR1 Ubiquitination Promotes mTORC1 Activation and Inhibits the Inflammation-Induced Colorectal Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Propionate promotes gluconeogenesis by regulating mechanistic target of rapamycin (mTOR) pathway in calf hepatocytes.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2023Article
- Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- Functional analysis reveals driver cooperativity and novel mechanisms in endometrial carcinogenesis.EMBO molecular medicine · 2023Article
- Role of FLCN Phosphorylation in Insulin-Mediated mTORC1 Activation and Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Sorafenib triggers ferroptosis via inhibition of HBXIP/SCD axis in hepatocellular carcinoma.Acta pharmacologica Sinica · 2023Article
- Cisplatin-induced cell death increases the degradation of the MRE11-RAD50-NBS1 complex through the autophagy/lysosomal pathway.Cell death and differentiation · 2023Article
- FBXW7 and human tumors: mechanisms of drug resistance and potential therapeutic strategies.Frontiers in pharmacology · 2023Review
- The mechanistic target of rapamycin complex 1 pathway involved in hepatic gluconeogenesis through peroxisome-proliferator-activated receptor γ coactivator-1Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2022Article
- Article
- Krüppel-like factor (KLF)5: An emerging foe of cardiovascular health.Journal of molecular and cellular cardiology · 2022Review
- Recent Insight on Regulations of FBXW7 and Its Role in Immunotherapy.Frontiers in oncology · 2022Review
- Arginine methyltransferase PRMT5 methylates and stabilizes KLF5 via decreasing its phosphorylation and ubiquitination to promote basal-like breast cancer.Cell death and differentiation · 2021Article
- Krüppel-like factor 5 is upregulated and induces cell proliferation in endometrial cancer.Oncology letters · 2021Article
- Function and regulation of F-box/WD repeat-containing protein 7.Oncology letters · 2020Review
- F-Box Proteins and Cancer.Cancers · 2020Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proproliferative transcription factor KLF5 plays an important role in promoting cell proliferation and tumorigenesis. KLF5 is a short-lived protein that can be rapidly degraded through the ubiquitin-proteasome pathway in cancer cells. However, the mechanisms regulating protein stability remain poorly understood. In this study, the tumor suppressor Fbw7, a component of the SCF complex (SCF(Fbw7)) E3 ubiquitin ligase, specifically promoted the degradation and ubiquitination of KLF5 but had little effect on the stability of KLF4. Fbw7 interacted with KLF5 in a CDC4 phosphodegron (CPD)-dependent manner. Three CPDs were found in the KLF5 protein. Simultaneous mutation of these CPDs significantly abolished Fbw7-mediated ubiquitination and degradation. Furthermore, Fbw7 deficiency dramatically delayed KLF5 turnover and led to the accumulation of KLF5 protein in cancer cells. Glycogen synthase kinase-3beta could phosphorylate and promote Fbw7-mediated KLF5 degradation. More importantly, Fbw7 negatively regulated the biological activity of KLF5 in gene regulation and cell proliferation. Taken together, these data indicate that Fbw7 is a key negative regulator controlling KLF5-mediated cell proliferation and suggest an additional mechanism linking the loss of Fbw7 function to tumorigenesis.
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