ArticleEMBO molecular medicine2013
p53's choice of myocardial death or survival: Oxygen protects infarct myocardium by recruiting p53 on NOS3 promoter through regulation of p53-Lys(118) acetylation.
Article in EMBO molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Ovarian tumor cells gain competitive advantage by actively reducing the cellular fitness of microenvironment cells.Nature biotechnology · 2025Article
- Ginsenoside Rb2 inhibits p300-mediated SF3A2 acetylation at lysine 10 to promote Fscn1 alternative splicing against myocardial ischemic/reperfusion injury.Journal of advanced research · 2024Article
- Post-translational modifications of pyruvate dehydrogenase complex in cardiovascular disease.iScience · 2024Review
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- The complexity of p53-mediated metabolic regulation in tumor suppression.Seminars in cancer biology · 2022Review
- Role of Posttranslational Modifications of Proteins in Cardiovascular Disease.Oxidative medicine and cellular longevity · 2022Review
- Transcription Factors Involved in the Development and Prognosis of Cardiac Remodeling.Frontiers in pharmacology · 2022Review
- The regulatory roles of p53 in cardiovascular health and disease.Cellular and molecular life sciences : CMLS · 2021Review
- Metabolic functions of the tumor suppressor p53: Implications in normal physiology, metabolic disorders, and cancer.Molecular metabolism · 2020Review
- HIF-transcribed p53 chaperones HIF-1α.Nucleic acids research · 2019Article
- Expression of miRNAs-122, -192 and -499 in end stage renal disease associated with acute myocardial infarction.Archives of medical science : AMS · 2019Article
- The Crosstalk between Acetylation and Phosphorylation: Emerging New Roles for HDAC Inhibitors in the Heart.International journal of molecular sciences · 2018Review
- Troponin T3 associates with DNA consensus sequence that overlaps with p53 binding motifs.Experimental gerontology · 2018Article
- The curcumin analog HO-3867 selectively kills cancer cells by converting mutant p53 protein to transcriptionally active wildtype p53.The Journal of biological chemistry · 2018Article
- Article
- No Evidence of Myocardial Oxygen Deprivation in Nonischemic Heart Failure.Circulation. Heart failure · 2015Article
- Co-expression of POU4F2/Brn-3b with p53 may be important for controlling expression of pro-apoptotic genes in cardiomyocytes following ischaemic/hypoxic insults.Cell death & disease · 2014Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Myocardial infarction, an irreversible cardiac tissue damage, involves progressive loss of cardiomyocytes due to p53-mediated apoptosis. Oxygenation is known to promote cardiac survival through activation of NOS3 gene. We hypothesized a dual role for p53, which, depending on oxygenation, can elicit apoptotic death signals or NOS3-mediated survival signals in the infarct heart. p53 exhibited a differential DNA-binding, namely, BAX-p53RE in the infarct heart or NOS3-p53RE in the oxygenated heart, which was regulated by oxygen-induced, post-translational modification of p53. In the infarct heart, p53 was heavily acetylated at Lys(118) residue, which was exclusively reversed in the oxygenated heart, apparently regulated by oxygen-dependent expression of TIP60. The inhibition of Lys(118) acetylation promoted the generation of NOS3-promoting prosurvival form of p53. Thus, oxygenation switches p53-DNA interaction by regulating p53 core-domain acetylation, promoting a prosurvival transcription activity of p53. Understanding this novel oxygen-p53 survival pathway will open new avenues in cardioprotection molecular therapy.
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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.