ArticleNucleic acids research2020
Deacetylase-independent function of SIRT6 couples GATA4 transcription factor and epigenetic activation against cardiomyocyte apoptosis.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 62 citations in OpenAlex.
- Post-translational modification of proteins in the human testis development pathway.Human reproduction update · 2026Review
- Ubiquitination degradation of GATA4 by CUL4B promotes ovarian cancer metastasis by inducing lysosomal acidification.Genome biology · 2026Article
- Transcriptional regulation in cardiovascular aging.Frontiers in cardiovascular medicine · 2026Review
- Sirtuin 6 mitigates thoracic aortic aneurysm progression via maintenance of mitochondria homeostasis in vascular smooth muscle cells.Acta pharmacologica Sinica · 2026Article
- The Role of Histone Methylation in Heart Failure: Epigenetic Mechanisms and Therapeutic Perspectives.Drug design, development and therapy · 2026Review
- Epigenetic Mechanisms in Heart Diseases.Reviews in cardiovascular medicine · 2025Review
- The role and mechanism of epigenetics in anticancer drug-induced cardiotoxicity.Basic research in cardiology · 2025Review
- SIRT6 regulates obesity-induced oxidative stress via ENDOG/SOD2 signaling in the heart.Cell biology and toxicology · 2023Article
- Tumor microenvironment-responsive spherical nucleic acid nanoparticles for enhanced chemo-immunotherapy.Journal of nanobiotechnology · 2023Article
- The Role of Histone Deacetylases in Acute Lung Injury-Friend or Foe.International journal of molecular sciences · 2023Review
- Sirtuin 6 is a key contributor to gender differences in acute kidney injury.Cell death discovery · 2023Article
- Sirt6 protects cardiomyocytes against doxorubicin-induced cardiotoxicity by inhibiting P53/Fas-dependent cell death and augmenting endogenous antioxidant defense mechanisms.Cell biology and toxicology · 2023Article
- The role of mammalian Sirtuin 6 in cardiovascular diseases and diabetes mellitus.Frontiers in physiology · 2023Review
- SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases.Aging and disease · 2022Review
- The histone deacetylase SIRT6 promotes glycolysis through the HIF-1α/HK2 signaling axis and induces erlotinib resistance in non-small cell lung cancer.Apoptosis : an international journal on programmed cell death · 2022Article
- SIRT6 Mitigates Heart Failure With Preserved Ejection Fraction in Diabetes.Circulation research · 2022Article
- Sirt6 deficiency contributes to mitochondrial fission and oxidative damage in podocytes via ROCK1-Drp1 signalling pathway.Cell proliferation · 2022Article
- Sirtuin 6 inhibition protects against glucocorticoid-induced skeletal muscle atrophy by regulating IGF/PI3K/AKT signaling.Nature communications · 2022Article
- SIRT6 Protects Against Myocardial Ischemia-Reperfusion Injury by Attenuating Aging-Related CHMP2B Accumulation.Journal of cardiovascular translational research · 2022Article
- SIRT6 in Vascular Diseases, from Bench to Bedside.Aging and disease · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SIRT6 deacetylase activity improves stress resistance via gene silencing and genome maintenance. Here, we reveal a deacetylase-independent function of SIRT6, which promotes anti-apoptotic gene expression via the transcription factor GATA4. SIRT6 recruits TIP60 acetyltransferase to acetylate GATA4 at K328/330, thus enhancing its chromatin binding capacity. In turn, GATA4 inhibits the deacetylase activity of SIRT6, thus ensuring the local chromatin accessibility via TIP60-promoted H3K9 acetylation. Significantly, the treatment of doxorubicin (DOX), an anti-cancer chemotherapeutic, impairs the SIRT6-TIP60-GATA4 trimeric complex, blocking GATA4 acetylation and causing cardiomyocyte apoptosis. While GATA4 hyperacetylation-mimic retains the protective effect against DOX, the hypoacetylation-mimic loses such ability. Thus, the data reveal a novel SIRT6-TIP60-GATA4 axis, which promotes the anti-apoptotic pathway to prevent DOX toxicity. Targeting the trimeric complex constitutes a new strategy to improve the safety of DOX chemotherapy in clinical application.
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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.