ArticleThe Journal of biological chemistry2009
Transcriptional corepressor SMILE recruits SIRT1 to inhibit nuclear receptor estrogen receptor-related receptor gamma transactivation.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 69 citations in OpenAlex.
- Stomach at the crossroads: nuclear receptor signaling at the interface between what we are and what we eat.Physiological reviews · 2026Review
- CREBZF/c-Jun modulates ApoE-mediated cholesterol transport to influence female steroid hormone synthesis.Zoological research · 2026Article
- Article
- Activation of estrogen-related receptor γ by calcium and cadmium.Frontiers in endocrinology · 2024Article
- Emerging Role of SMILE in Liver Metabolism.International journal of molecular sciences · 2023Review
- Molecular dynamics of the ERRγ ligand-binding domain bound with agonist and inverse agonist.PloS one · 2023Article
- Epigallocatechin-3-Gallate Suppresses BMP-6-Mediated SMAD1/5/8 Transactivation of Hepcidin Gene by Inducing SMILE in Hepatocytes.Antioxidants (Basel, Switzerland) · 2021Article
- Metformin-Inducible Small Heterodimer Partner Interacting Leucine Zipper Protein Ameliorates Intestinal Inflammation.Frontiers in immunology · 2021Article
- GSK5182, 4-Hydroxytamoxifen Analog, a New Potential Therapeutic Drug for Osteoarthritis.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Orphan Nuclear Receptor ERRγ Is a Novel Transcriptional Regulator of IL-6 Mediated Hepatic BMP6 Gene Expression in Mice.International journal of molecular sciences · 2020Article
- Article
- Epigallocatechin-3-Gallate (EGCG)-Inducible SMILE Inhibits STAT3-Mediated Hepcidin Gene Expression.Antioxidants (Basel, Switzerland) · 2020Article
- An inverse agonist of estrogen-related receptor γ regulates 2-arachidonoylglycerol synthesis by modulating diacylglycerol lipase expression in alcohol-intoxicated mice.Archives of toxicology · 2020Article
- The SMILE transcriptional corepressor inhibits cAMP response element-binding protein (CREB)-mediated transactivation of gluconeogenic genes.The Journal of biological chemistry · 2018Article
- The Orphan Nuclear Receptor ERRγ Regulates Hepatic CB1 Receptor-Mediated Fibroblast Growth Factor 21 Gene Expression.PloS one · 2016Article
- Orphan nuclear receptor oestrogen-related receptor γ (ERRγ) plays a key role in hepatic cannabinoid receptor type 1-mediated induction of CYP7A1 gene expression.The Biochemical journal · 2015Article
- Sirtuins in epigenetic regulation.Chemical reviews · 2015Review
- Ursodeoxycholic acid inhibits liver X receptor α-mediated hepatic lipogenesis via induction of the nuclear corepressor SMILE.The Journal of biological chemistry · 2014Article
- Effects of cyclic AMP response element binding protein-Zhangfei (CREBZF) on the unfolded protein response and cell growth are exerted through the tumor suppressor p53.Cell cycle (Georgetown, Tex.) · 2014Article
- Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SMILE (small heterodimer partner interacting leucine zipper protein) has been identified as a corepressor of the glucocorticoid receptor, constitutive androstane receptor, and hepatocyte nuclear factor 4alpha. Here we show that SMILE also represses estrogen receptor-related receptor gamma (ERRgamma) transactivation. Knockdown of SMILE gene expression increases ERRgamma activity. SMILE directly interacts with ERRgamma in vitro and in vivo. Domain mapping analysis showed that SMILE binds to the AF2 domain of ERRgamma. SMILE represses ERRgamma transactivation partially through competition with coactivators PGC-1alpha, PGC-1beta, and GRIP1. Interestingly, the repression of SMILE on ERRgamma is released by SIRT1 inhibitors, a catalytically inactive SIRT1 mutant, and SIRT1 small interfering RNA but not by histone protein deacetylase inhibitor. In vivo glutathione S-transferase pulldown and coimmunoprecipitation assays validated that SMILE physically interacts with SIRT1. Furthermore, the ERRgamma inverse agonist GSK5182 enhances the interaction of SMILE with ERRgamma and SMILE-mediated repression. Knockdown of SMILE or SIRT1 blocks the repressive effect of GSK5182. Moreover, chromatin immunoprecipitation assays revealed that GSK5182 augments the association of SMILE and SIRT1 on the promoter of the ERRgamma target PDK4. GSK5182 and adenoviral overexpression of SMILE cooperate to repress ERRgamma-induced PDK4 gene expression, and this repression is released by overexpression of a catalytically defective SIRT1 mutant. Finally, we demonstrated that ERRgamma regulates SMILE gene expression, which in turn inhibits ERRgamma. Overall, these findings implicate SMILE as a novel corepressor of ERRgamma and recruitment of SIRT1 as a novel repressive mechanism for SMILE and ERRgamma inverse agonist.
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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.