ArticleOncogene2013
GSK3β phosphorylation of the KLF6 tumor suppressor promotes its transactivation of p21.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 40 citations in OpenAlex.
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- Prediction of Potential Biomarkers in Early-Stage Nasopharyngeal Carcinoma Based on Platelet RNA Sequencing.Molecular biotechnology · 2023Article
- KLF6 facilitates differentiation of odontoblasts through modulating the expression of P21 in vitro.International journal of oral science · 2022Article
- Differential microRNA profiles of intramuscular and secreted extracellular vesicles in human tissue-engineered muscle.Frontiers in physiology · 2022Article
- LncRNAs in the Regulation of Genes and Signaling Pathways through miRNA-Mediated and Other Mechanisms in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2021Review
- Glycogen Synthase Kinase 3 Beta Regulates the Human Aryl Hydrocarbon Receptor Cellular Content and Activity.International journal of molecular sciences · 2021Article
- lncRNA OR3A4 Promotes the Proliferation and Metastasis of Ovarian Cancer Through KLF6 Pathway.Frontiers in pharmacology · 2021Article
- Glycogen synthase kinase 3β in tumorigenesis and oncotherapy (Review).Oncology reports · 2020Review
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- Hotspot mutant p53-R273H inhibits KLF6 expression to promote cell migration and tumor metastasis.Cell death & disease · 2020Article
- GSK-3 is an RNA polymerase II phospho-CTD kinase.Nucleic acids research · 2020Article
- Upregulated miRNA-543 promotes the proliferation and migration of gastric carcinoma by downregulating KLF6.American journal of translational research · 2020Article
- Autophagy induces G0/G1 arrest and apoptosis in menstrual blood-derived endometrial stem cells via GSK3-β/β-catenin pathway.Stem cell research & therapy · 2018Article
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- AMPK/FIS1-Mediated Mitophagy Is Required for Self-Renewal of Human AML Stem Cells.Cell stem cell · 2018Article
- R-Ras-Akt axis induces endothelial lumenogenesis and regulates the patency of regenerating vasculature.Nature communications · 2017Article
- Krüppel-like factor 6 is a transcriptional activator of autophagy in acute liver injury.Scientific reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
KLF6, a ubiquitously expressed Krüppel-like transcription factor, is frequently inactivated in human cancer and has significant roles in cellular proliferation, apoptosis, differentiation and development. A key mechanism of KLF6-mediated growth suppression is through p53-independent transactivation of p21. Several cancer-derived KLF6 mutants lead to the loss of p21-mediated growth suppression through an unknown mechanism. Because several colorectal cancer and hepatocellular carcinoma-derived KLF6 mutations affect a glycogen synthase kinase 3β (GSK3β) phosphorylation consensus site, we investigated the role of GSK3β in the regulation of KLF6 function. Based on transient transfection, GSK3β augments the transactivation of a p21 promoter luciferase by KLF6. Reciprocal co-immunoprecipitation of hemagglutinin (HA)-GSK3β and Flag-KLF6 validated the interaction between these two proteins. KLF6 phosphorylation is augmented in the presence of GSK3β based on in vitro and in vivo (32)P incorporation assays. Site-directed mutagenesis of the candidate phosphorylation sites to alanines ('KLF6-4A' phosphomutant) eliminated a higher molecular weight phosphorylated isoform of KLF6 based on western blot. GSK3β augmented the transactivation by wild-type KLF6, but not KLF6-4A, towards the p21 promoter, and increased p21 protein. Functionally, GSK3β enhanced KLF6-mediated growth suppression, which was abrogated by the KLF6-4A phosphomutant. These data establish that GSK3β directly phosphorylates KLF6, which augments its induction of p21 and resultant growth suppression. This interaction may account for the growth-promoting effects of cancer-derived KLF6 mutants that lack tumor suppressor activity.
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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.