ArticlePloS one2017
Cardiac-specific ablation of the E3 ubiquitin ligase Mdm2 leads to oxidative stress, broad mitochondrial deficiency and early death.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 43 citations in OpenAlex.
- Role of the MDM2/p53 axis in regulating cisplatin response in tumor cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Ubiquitin E3 Ligases and p53 in Doxorubicin-Induced Cardiotoxicity.International journal of molecular sciences · 2025Review
- Mechanisms of high-glucose-induced mitochondrial damage and glycolipid accumulation in largemouth bass.Journal of animal science and biotechnology · 2025Article
- Peroxisome Proliferator-Activated Receptor Family of Lipid-Activated Nuclear Receptors Alpha Silencing Promotes Oxidative Stress and Hypertrophic Phenotype in Rat Cardiac Cells.Antioxidants (Basel, Switzerland) · 2025Article
- The MDM2 SNP309 differentially impacts cardiorespiratory fitness in young healthy women and men.European journal of applied physiology · 2025Article
- Dynamic map illuminates Hippo-cMyc module crosstalk driving cardiomyocyte proliferation.Development (Cambridge, England) · 2025Article
- Diacylglycerol Kinase ζ Attenuates Doxorubicin-Induced Cardiotoxicity Through p53 Degradation.Journal of the American Heart Association · 2025Article
- Cdk1 Deficiency Extends the Postnatal Window of Cardiomyocyte Proliferation and Restores Cardiac Function after Myocardial Infarction.International journal of molecular sciences · 2024Article
- Ubiquitin ligase MDM2 mediates endothelial inflammation in Kawasaki disease vasculitis development.Translational pediatrics · 2024Article
- Xinnaotongluo liquid protects H9c2 cells from H/R-induced damage by regulating MDM2/STEAP3.PloS one · 2024Article
- E3 ubiquitin ligases: key regulators of osteogenesis and potential therapeutic targets for bone disorders.Frontiers in cell and developmental biology · 2024Review
- MDM2 Regulation of HIF Signaling Causes Microvascular Dysfunction in Hypertrophic Cardiomyopathy.Circulation · 2023Article
- Spleen tyrosine kinase (SYK) signals are implicated in cardio-cerebrovascular diseases.Heliyon · 2023Review
- p53 and Myofibroblast Apoptosis in Organ Fibrosis.International journal of molecular sciences · 2023Review
- Shenqi Lixin Decoction improves cardiac function in rats with adriamycin-induced heart failure through modulation of PGC-1α and mitochondrial apoptosis pathway.Annals of translational medicine · 2021Article
- Inhibiting the Pkm2/b-catenin axis drives in vivo replication of adult cardiomyocytes following experimental MI.Cell death and differentiation · 2021Article
- Under construction: The dynamic assembly, maintenance, and degradation of the cardiac sarcomere.Journal of molecular and cellular cardiology · 2020Review
- Regulation of cardiovascular calcium channel activity by post-translational modifications or interacting proteins.Pflugers Archiv : European journal of physiology · 2020Review
- Targeting MDM2 for novel molecular therapy: Beyond oncology.Medicinal research reviews · 2020Review
- Mdm2 enhances ligase activity of parkin and facilitates mitophagy.Scientific reports · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The maintenance of normal heart function requires proper control of protein turnover. The ubiquitin-proteasome system is a principal regulator of protein degradation. Mdm2 is the main E3 ubiquitin ligase for p53 in mitotic cells thereby regulating cellular growth, DNA repair, oxidative stress and apoptosis. However, which of these Mdm2-related activities are preserved in differentiated cardiomyocytes has yet to be determined. We sought to elucidate the role of Mdm2 in the control of normal heart function. We observed markedly reduced Mdm2 mRNA levels accompanied by highly elevated p53 protein expression in the hearts of wild type mice subjected to myocardial infarction or trans-aortic banding. Accordingly, we generated conditional cardiac-specific Mdm2 gene knockout (Mdm2f/f;mcm) mice. In adulthood, Mdm2f/f;mcm mice developed spontaneous cardiac hypertrophy, left ventricular dysfunction with early mortality post-tamoxifen. A decreased polyubiquitination of myocardial p53 was observed, leading to its stabilization and activation, in the absence of acute stress. In addition, transcriptomic analysis of Mdm2-deficient hearts revealed that there is an induction of E2f1 and c-Myc mRNA levels with reduced expression of the Pgc-1a/Ppara/Esrrb/g axis and Pink1. This was associated with a significant degree of cardiomyocyte apoptosis, and an inhibition of redox homeostasis and mitochondrial bioenergetics. All these processes are early, Mdm2-associated events and contribute to the development of pathological hypertrophy. Our genetic and biochemical data support a role for Mdm2 in cardiac growth control through the regulation of p53, the Pgc-1 family of transcriptional coactivators and the pivotal antioxidant Pink1.
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.