ArticleThe Journal of biological chemistry2018
The SMILE transcriptional corepressor inhibits cAMP response element-binding protein (CREB)-mediated transactivation of gluconeogenic genes.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Hypoxia Promotes Gluconeogenesis Through PGC-1α in the Liver of Lasiopodomys brandtii.Integrative zoology · 2026Article
- Regulation and clinical manifestations of gluconeogenesis dysfunction.npj metabolic health and disease · 2026Review
- Ulcerative colitis, pathophysiological mechanisms and drug repurposing: a new therapeutic dawn-narrative review.Inflammopharmacology · 2026Review
- Nutritional and hormonal regulation of mitochondrial biogenesis drives fat body remodeling for reproductive competence.Journal of advanced research · 2026Article
- Evaluation of Hypoglycemic Polyphenolic Compounds in Blueberry Extract: Functional Effects and Mechanisms.Antioxidants (Basel, Switzerland) · 2024Article
- Intrauterine hyperglycaemia during late gestation caused mitochondrial dysfunction in skeletal muscle of male offspring through CREB/PGC1A signaling.Nutrition & diabetes · 2024Article
- Qiliqiangxin capsule alleviates cardiac hypertrophy and cardiac dysfunction by regulating miR-382-5p/ATF3 axis.Clinics (Sao Paulo, Brazil) · 2024Article
- Modulating glucocorticoid receptor actions in physiology and pathology: Insights from coregulators.Pharmacology & therapeutics · 2023Review
- MLK4 promotes glucose metabolism in lung adenocarcinoma through CREB-mediated activation of phosphoenolpyruvate carboxykinase and is regulated by KLF5.Oncogenesis · 2023Article
- Hepatic ZBTB22 promotes hyperglycemia and insulin resistance via PEPCK1-driven gluconeogenesis.EMBO reports · 2023Article
- Circular RNA Tmcc1 improves astrocytic glutamate metabolism and spatial memory via NF-κB and CREB signaling in a bile duct ligation mouse model: transcriptional and cellular analyses.Journal of neuroinflammation · 2023Article
- Small heterodimer partner interacting leucine zipper protein (SMILE) ameliorates autoimmune arthritis via AMPK signaling pathway and the regulation of B cell activation.Cell communication and signaling : CCS · 2023Article
- Emerging Role of SMILE in Liver Metabolism.International journal of molecular sciences · 2023Review
- SMILE Downregulation during Melanogenesis Induces MITF Transcription in B16F10 Cells.International journal of molecular sciences · 2022Article
- Oxidative Stress, Genomic Integrity, and Liver Diseases.Molecules (Basel, Switzerland) · 2022Review
- Metabolic and Microbiome Alterations Following the Enrichment of a High-Fat Diet With High Oleic Acid Peanuts Versus the Traditional Peanuts Cultivar in Mice.Frontiers in nutrition · 2022Article
- Circ_nuclear factor I X (circNfix) attenuates pressure overload-induced cardiac hypertrophy via regulating miR-145-5p/ATF3 axis.Bioengineered · 2021Article
- Epigallocatechin-3-Gallate Suppresses BMP-6-Mediated SMAD1/5/8 Transactivation of Hepcidin Gene by Inducing SMILE in Hepatocytes.Antioxidants (Basel, Switzerland) · 2021Article
- Skeleton interoception regulates bone and fat metabolism through hypothalamic neuroendocrine NPY.eLife · 2021Article
- Lyophilized Maqui (Antioxidants (Basel, Switzerland) · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Under fasting conditions, activation of several hepatic genes sets the stage for gluconeogenesis in the liver. cAMP response element-binding protein (CREB), CREB-regulated transcription coactivator 2 (CRTC2), and peroxisome proliferator-activated receptor γ coactivator 1-alpha (PGC-1α) are essential for this transcriptional induction of gluconeogenic genes. PGC-1α induction is mediated by activation of a CREB/CRTC2 signaling complex, and recent findings have revealed that small heterodimer partner-interacting leucine zipper protein (SMILE), a member of the CREB/ATF family of basic region-leucine zipper (bZIP) transcription factors, is an insulin-inducible corepressor that decreases PGC-1α expression and abrogates its stimulatory effect on hepatic gluconeogenesis. However, the molecular mechanism whereby SMILE suppresses PGC-1α expression is unknown. Here, we investigated SMILE's effects on the CREB/CRTC2 signaling pathway and glucose metabolism. We found that SMILE significantly inhibits CREB/CRTC2-induced PGC-1α expression by interacting with and disrupting the CREB/CRTC2 complex. Consequently, SMILE decreased PGC-1α-induced hepatic gluconeogenic gene expression. Furthermore, SMILE inhibited CREB/CRTC2-induced phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene expression by directly repressing the expression of these genes and by indirectly inhibiting the expression of PGC-1α via CREB/CRTC2 repression. Indeed, enhanced gluconeogenesis and circulating blood glucose levels in mice injected with an adenovirus construct containing a constitutively active CRTC2 variant (CRTC2-S171A) were significantly reduced by WT SMILE, but not by leucine zipper-mutated SMILE. These results reveal that SMILE represses CREB/CRTC2-induced PGC-1α expression, an insight that may help inform potential therapeutic approaches targeting PGC-1α-mediated regulation of hepatic glucose metabolism.
Indexed as
Identifiers
What OpenQuestion holds
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.