ArticleProceedings of the National Academy of Sciences of the United States of America2000
DAF-16 recruits the CREB-binding protein coactivator complex to the insulin-like growth factor binding protein 1 promoter in HepG2 cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 165 citations in OpenAlex.
- Recognition of two hydrophobic pockets in the KIX domain of CBP by FOXO4 transactivation domain.Communications biology · 2025Article
- Three isoforms ofmicroPublication biology · 2025Article
- Methods to Study Structure and Dynamics of FOXO Proteins.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Acetylation of FOXO1 activates Bim expression involved in CVB3 induced cardiomyocyte apoptosis.Apoptosis : an international journal on programmed cell death · 2024Article
- Forkhead box O proteins: steering the course of stem cell fate.Cell regeneration (London, England) · 2024Review
- Article
- The CBP-1/p300 Lysine Acetyltransferase Regulates the Heat Shock Response inFrontiers in aging · 2022Article
- Histone acetylation promotes long-lasting defense responses and longevity following early life heat stress.PLoS genetics · 2019Article
- Regulation of cellular senescence via the FOXO4-p53 axis.FEBS letters · 2018Review
- Dietary Restriction and Glycolytic Inhibition Reduce Proteotoxicity and Extend Lifespan via NHR-49.Current neurobiology · 2018Article
- FOXO in Neural Cells and Diseases of the Nervous System.Current topics in developmental biology · 2018Review
- Article
- Loss of Interdependent Binding by the FoxO1 and FoxA1/A2 Forkhead Transcription Factors Culminates in Perturbation of Active Chromatin Marks and Binding of Transcriptional Regulators at Insulin-sensitive Genes.The Journal of biological chemistry · 2016Article
- Redox regulation of FoxO transcription factors.Redox biology · 2015Review
- Article
- Two potential hookworm DAF-16 target genes, SNR-3 and LPP-1: gene structure, expression profile, and implications of a cis-regulatory element in the regulation of gene expression.Parasites & vectors · 2015Article
- Activation of Foxo1 by insulin resistance promotes cardiac dysfunction and β-myosin heavy chain gene expression.Circulation. Heart failure · 2015Article
- Systems pharmacology of adiposity reveals inhibition of EP300 as a common therapeutic mechanism of caloric restriction and resveratrol for obesity.Frontiers in pharmacology · 2015Article
- Novel mechanism of blood pressure regulation by forkhead box class O1-mediated transcriptional control of hepatic angiotensinogen.Hypertension (Dallas, Tex. : 1979) · 2014Article
- USP7 attenuates hepatic gluconeogenesis through modulation of FoxO1 gene promoter occupancy.Molecular endocrinology (Baltimore, Md.) · 2014Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Insulin negatively regulates expression of the insulin-like growth factor binding protein 1 (IGFBP-1) gene by means of an insulin-responsive element (IRE) that also contributes to glucocorticoid stimulation of this gene. We find that the Caenorhabditis elegans protein DAF-16 binds the IGFBP-1 small middle dotIRE with specificity similar to that of the forkhead (FKH) factor(s) that act both to enhance glucocorticoid responsiveness and to mediate the negative effect of insulin at this site. In HepG2 cells, DAF-16 and its mammalian homologs, FKHR, FKHRL1, and AFX, activate transcription through the IGFBP-1.IRE; this effect is inhibited by the viral oncoprotein E1A, but not by mutants of E1A that fail to interact with the coactivator p300/CREB-binding protein (CBP). We show that DAF-16 and FKHR can interact with both the KIX and E1A/SRC interaction domains of p300/CBP, as well as the steroid receptor coactivator (SRC). A C-terminal deletion mutant of DAF-16 that is nonfunctional in C. elegans fails to bind the KIX domain of CBP, fails to activate transcription through the IGFBP-1.IRE, and inhibits activation of the IGFBP-1 promoter by glucocorticoids. Thus, the interaction of DAF-16 homologs with the KIX domain of CBP is essential to basal and glucocorticoid-stimulated transactivation. Although AFX interacts with the KIX domain of CBP, it does not interact with SRC and does not respond to glucocorticoids or insulin. Thus, we conclude that DAF-16 and FKHR act as accessory factors to the glucocorticoid response, by recruiting the p300/CBP/SRC coactivator complex to an FKH factor site in the IGFBP-1 promoter, which allows the cell to integrate the effects of glucocorticoids and insulin on genes that carry this site.
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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.