ArticlePloS one2012
Gene expression of the tumour suppressor LKB1 is mediated by Sp1, NF-Y and FOXO transcription factors.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Insights into targeting LKB1 in tumorigenesis.Genes & diseases · 2025Review
- LKB1 biology: assessing the therapeutic relevancy of LKB1 inhibitors.Cell communication and signaling : CCS · 2024Review
- Integrative Proteomic and Phosphoproteomic Analyses Revealed Complex Mechanisms Underlying Reproductive Diapause inInsects · 2022Article
- A metabolic switch regulates the transition between growth and diapause in C. elegans.BMC biology · 2020Article
- SIRT1 inhibits chemoresistance and cancer stemness of gastric cancer by initiating an AMPK/FOXO3 positive feedback loop.Cell death & disease · 2020Article
- AMPK in skeletal muscle function and metabolism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Review
- Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health.Journal of nutrition and metabolism · 2018Review
- The FOXO3/PGC-1β signaling axis is essential for cancer stem cell properties of pancreatic ductal adenocarcinoma.The Journal of biological chemistry · 2017Article
- Transcription factor NF‑YA promotes a malignant phenotype by upregulating fatty acid synthase expression.Molecular medicine reports · 2016Article
- Establishment of an Immortalized Skin Keratinocyte Cell Line Derived from the Animal Model Mastomys coucha.PloS one · 2016Article
- Community Structure Reveals Biologically Functional Modules in MEF2C Transcriptional Regulatory Network.Frontiers in physiology · 2016Article
- Deciphering Signaling Pathway Networks to Understand the Molecular Mechanisms of Metformin Action.PLoS computational biology · 2015Article
- MicroRNA-17 promotes normal ovarian cancer cells to cancer stem cells development via suppression of the LKB1-p53-p21/WAF1 pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Identification and Functional Characterization of Novel Genetic Variations in the OCTN1 Promoter.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2014Article
- DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans.PLoS genetics · 2014Article
- Transcription factor NF-Y is a functional regulator of the transcription of core clock gene Bmal1.The Journal of biological chemistry · 2013Article
- The estrogen receptor α is the key regulator of the bifunctional role of FoxO3a transcription factor in breast cancer motility and invasiveness.Cell cycle (Georgetown, Tex.) · 2013Article
- Nutrient-sensing pathways and metabolic regulation in stem cells.The Journal of cell biology · 2013Review
- Forkhead box proteins: tuning forks for transcriptional harmony.Nature reviews. Cancer · 2013Review
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Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serine/threonine kinase LKB1 is a tumour suppressor that regulates multiple biological pathways, including cell cycle control, cell polarity and energy metabolism by direct phosphorylation of 14 different AMP-activated protein kinase (AMPK) family members. Although many downstream targets have been described, the regulation of LKB1 gene expression is still poorly understood. In this study, we performed a functional analysis of the human LKB1 upstream regulatory region. We used 200 base pair deletion constructs of the 5'-flanking region fused to a luciferase reporter to identify the core promoter. It encompasses nucleotides -345 to +52 relative to the transcription start site and coincides with a DNase I hypersensitive site. Based on extensive deletion and substitution mutant analysis of the LKB1 promoter, we identified four cis-acting elements which are critical for transcriptional activation. Using electrophoretic mobility shift assays as well as chromatin immunoprecipitations, we demonstrate that the transcription factors Sp1, NF-Y and two forkhead box O (FOXO) family members FOXO3 and FOXO4 bind to these elements. Overexpression of these factors significantly increased the LKB1 promoter activity. Conversely, small interfering RNAs directed against NF-Y alpha and the two FOXO proteins greatly reduced endogenous LKB1 expression and phosphorylation of LKB1's main substrate AMPK in three different cell lines. Taken together, these results demonstrate that Sp1, NF-Y and FOXO transcription factors are involved in the regulation of LKB1 transcription.
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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.