ArticleThe EMBO journal2004
Activation of cardiac Cdk9 represses PGC-1 and confers a predisposition to heart failure.
Article in The EMBO journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
What it found
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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.
The trial behind it
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Who cites it
71 citing papers in PubMed, 158 citations in OpenAlex.
- Article
- Circulating PGC-1α and MOTS-c Peptide as Potential Mitochondrial Biomarkers in Patients Undergoing Aortic Valve Replacement.Biologics : targets & therapy · 2025Article
- The diagnostic value investigation of programmed cell death genes in heart failure.BMC cardiovascular disorders · 2024Article
- The Pleiotropic Face of CREB Family Transcription Factors.Molecules and cells · 2023Review
- Cirrhotic Cardiomyopathy Following Bile Duct Ligation in Rats-A Matter of Time?International journal of molecular sciences · 2023Article
- Therapeutic Hypothermia Inhibits Hypoxia-Induced Cardiomyocyte Apoptosis Via the MiR-483-3p/Cdk9 Axis.Journal of the American Heart Association · 2023Article
- Targeting transcription in heart failure via CDK7/12/13 inhibition.Nature communications · 2022Article
- Pyrazole-Curcumin Suppresses Cardiomyocyte Hypertrophy by Disrupting the CDK9/CyclinT1 Complex.Pharmaceutics · 2022Article
- HRas and Myc synergistically induce cell cycle progression and apoptosis of murine cardiomyocytes.Frontiers in cardiovascular medicine · 2022Article
- Review
- CDK9 keeps RNA polymerase II on track.Cellular and molecular life sciences : CMLS · 2021Review
- Cyclin-Dependent Kinases (CDK) and Their Role in Diseases Development-Review.International journal of molecular sciences · 2021Review
- A Transgenic Mouse Model of Eccentric Left Ventricular Hypertrophy With Preserved Ejection Fraction Exhibits Alterations in the Autophagy-Lysosomal Pathway.Frontiers in physiology · 2021Article
- In Vitro and In Vivo Effects of Fermented Oyster-Derived Lactate on Exercise Endurance Indicators in Mice.International journal of environmental research and public health · 2020Article
- Melatonin-Induced PGC-1α Improves Angiogenic Potential of Mesenchymal Stem Cells in Hindlimb Ischemia.Biomolecules & therapeutics · 2020Article
- Reactivation of Myc transcription in the mouse heart unlocks its proliferative capacity.Nature communications · 2020Article
- Multiple Levels of PGC-1α Dysregulation in Heart Failure.Frontiers in cardiovascular medicine · 2020Review
- Metabolic Alterations in Inherited Cardiomyopathies.Journal of clinical medicine · 2019Review
- Targeting CDK9 for treatment of colorectal cancer.Molecular oncology · 2019Article
- Targeting transcriptional machinery to inhibit enhancer-driven gene expression in heart failure.Heart failure reviews · 2019Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypertrophy allows the heart to adapt to workload but culminates in later pump failure; how it is achieved remains uncertain. Previously, we showed that hypertrophy is accompanied by activation of cyclin T/Cdk9, which phosphorylates the C-terminal domain of the large subunit of RNA polymerase II, stimulating transcription elongation and pre-mRNA processing; Cdk9 activity was required for hypertrophy in culture, whereas heart-specific activation of Cdk9 by cyclin T1 provoked hypertrophy in mice. Here, we report that alphaMHC-cyclin T1 mice appear normal at baseline yet suffer fulminant apoptotic cardiomyopathy when challenged by mechanical stress or signaling by the G-protein Gq. At pathophysiological levels, Cdk9 activity suppresses many genes for mitochondrial proteins including master regulators of mitochondrial function (peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1), nuclear respiratory factor-1). In culture, cyclin T1/Cdk9 suppresses PGC-1, decreases mitochondrial membrane potential, and sensitizes cardiomyocytes to apoptosis, effects rescued by exogenous PGC-1. Cyclin T1/Cdk9 inhibits PGC-1 promoter activity and preinitiation complex assembly. Thus, chronic activation of Cdk9 causes not only cardiomyocyte enlargement but also defective mitochondrial function, via diminished PGC-1 transcription, and a resulting susceptibility to apoptotic cardiomyopathy.
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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.