ArticleNature medicine2012
The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac hypertrophy by targeting c-Jun.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 245 papers.
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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.
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Who cites it
245 citing papers in PubMed, 471 citations in OpenAlex.
- Targeting mitochondrial morphofunctional homeostasis and oxidative stress: Iristectorigenin A protects against cardiac remodeling via SIRT6/FOXO1 signaling.Acta pharmacologica Sinica · 2026Article
- Review
- Conserved Transcriptomic Signatures of Sirt6 Activity: A Cross-Species RNA-seq Meta-analysis.bioRxiv : the preprint server for biology · 2026Article
- USP11 alleviates pathological cardiac hypertrophy via stabilizing SIRT6.Cellular and molecular life sciences : CMLS · 2026Article
- Sirtuins in Medicine: Multifaceted Roles in Physiological Processes and Cardiovascular Diseases.Biomolecules · 2026Review
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Integrative multi-omics analysis of macrophage polarization-related genes in atherosclerosis development.Clinical epigenetics · 2026Article
- Metabolic-epigenetic axis in cardiovascular inflammatory injury: regulatory mechanisms and intervention strategies.Frontiers in cardiovascular medicine · 2026Review
- Transcriptional regulation in cardiovascular aging.Frontiers in cardiovascular medicine · 2026Review
- Post-translational acylation of proteins in cardiac hypertrophy.Nature reviews. Cardiology · 2025Review
- Inhibitory Effect of Sirtuin6 on EndMT by Regulating Oxidative Stress and Autophagy in Coxsackievirus B3-Induced Cardiac Endothelial Cells.Immunity, inflammation and disease · 2025Article
- Emerging epigenetic modifications in renal fibrosis: From mechanisms to treatments.Acta pharmaceutica Sinica. B · 2025Review
- The Sirt3-CD38 axis induces mitochondrial dysfunction in hypertrophied heart by regulating mitochondrial calcium overload.European journal of medical research · 2025Article
- Cadmium exposure triggers vimentin phosphorylation via SIRT6-regulated AKT/PI3K signaling pathway in COPD.European journal of cell biology · 2025Article
- Glucocorticoid-Mediated Skeletal Muscle Atrophy: Molecular Mechanisms and Potential Therapeutic Targets.International journal of molecular sciences · 2025Review
- Contribution of histone deacetylases (HDACs) to the regulation of histone and non-histone proteins: implications for fibrotic diseases.BMB reports · 2025Review
- HDACs and Their Inhibitors on Post-Translational Modifications: The Regulation of Cardiovascular Disease.Cells · 2025Review
- Stereopy: modeling comparative and spatiotemporal cellular heterogeneity via multi-sample spatial transcriptomics.Nature communications · 2025Article
- Sirtuins and Resveratrol in Cardiorenal Diseases: A Narrative Review of Mechanisms and Therapeutic Potential.Nutrients · 2025Review
- Activation and inhibition of sirtuins: From bench to bedside.Medicinal research reviews · 2025Review
185 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
Abstract
Abnormal activation of insulin-like growth factor (IGF)-Akt signaling is implicated in the development of various diseases, including heart failure. However, the molecular mechanisms that regulate activation of this signaling pathway are not completely understood. Here we show that sirtuin 6 (SIRT6), a nuclear histone deacetylase, functions at the level of chromatin to directly attenuate IGF-Akt signaling. SIRT6-deficient mice developed cardiac hypertrophy and heart failure, whereas SIRT6 transgenic mice were protected from hypertrophic stimuli, indicating that SIRT6 acts as a negative regulator of cardiac hypertrophy. SIRT6-deficient mouse hearts showed hyperactivation of IGF signaling-related genes and their downstream targets. Mechanistically, SIRT6 binds to and suppresses the promoter of IGF signaling-related genes by interacting with c-Jun and deacetylating histone 3 at Lys9 (H3K9). We also found reduced SIRT6 expression in human failing hearts. These findings disclose a new link between SIRT6 and IGF-Akt signaling and implicate SIRT6 in the development of cardiac hypertrophy and failure.
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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.