ArticleMolecular and cellular biology2000
Proteasome-mediated degradation of the coactivator p300 impairs cardiac transcription.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 106 citations in OpenAlex.
- Downregulation of MLF1 safeguards cardiomyocytes against senescence-associated chromatin opening.Nucleic acids research · 2025Article
- p300 in Cardiac Development and Accelerated Cardiac Aging.Aging and disease · 2020Review
- Proteasome inhibition creates a chromatin landscape favorable to RNA Pol II processivity.The Journal of biological chemistry · 2020Article
- Review
- Article
- YB-1 transforms human mammary epithelial cells through chromatin remodeling leading to the development of basal-like breast cancer.Stem cells (Dayton, Ohio) · 2014Article
- Regulation of histone modifying enzymes by the ubiquitin-proteasome system.Biochimica et biophysica acta · 2014Review
- Epigenetic regulation of cardiac myocyte differentiation.Frontiers in genetics · 2014Review
- Article
- Resveratrol improves cardiomyopathy in dystrophin-deficient mice through SIRT1 protein-mediated modulation of p300 protein.The Journal of biological chemistry · 2013Article
- BRMS1 suppresses lung cancer metastases through an E3 ligase function on histone acetyltransferase p300.Cancer research · 2013Article
- p38 MAPK- and Akt-mediated p300 phosphorylation regulates its degradation to facilitate nucleotide excision repair.Nucleic acids research · 2013Article
- Cardiac systolic dysfunction in doxorubicin-challenged rats is associated with upregulation of MuRF2 and MuRF3 E3 ligases.Experimental and clinical cardiology · 2012Article
- Vascular smooth muscle cell phenotypic plasticity: focus on chromatin remodelling.Cardiovascular research · 2012Review
- A novel non-canonical mechanism of regulation of MST3 (mammalian Sterile20-related kinase 3).The Biochemical journal · 2012Article
- Article
- Mass spectrometric studies on epigenetic interaction networks in cell differentiation.The Journal of biological chemistry · 2011Article
- Stem cell protein Piwil2 modulates chromatin modifications upon cisplatin treatment.Mutation research · 2011Article
- Promoter context determines the role of proteasome in ligand-dependent occupancy of retinoic acid responsive elements.Epigenetics · 2011Article
- Chromatin remodeling pathways in smooth muscle cell differentiation, and evidence for an integral role for p300.PloS one · 2010Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription of tissue-specific genes is controlled by regulatory factors and cofactors and is suppressed in cardiac cells by the antineoplastic agent doxorubicin. Here we show that exposure of cultured cardiomyocytes to doxorubicin resulted in the rapid depletion of transcripts for MEF2C, dHAND, and NKX2.5, three pivotal regulators of cardiac gene expression. Delivery of exogenous p300, a coactivator of MEF2C and NKX2.5 in cardiomyocytes, restored cardiac transcription despite the presence of doxorubicin. Furthermore, p300 also restored the accumulation of transcripts for MEF2C itself. Importantly, cardiocytes exposed to doxorubicin displayed reduced levels of p300 proteins. This was not due to alterations in the level of p300 transcripts; rather, and surprisingly, doxorubicin promoted selective degradation of p300 mediated by the 26S-proteasome machinery. Doxorubicin had no effect on the general level of ubiquitinated proteins or on the levels of beta-catenin, a protein known to be degraded by proteasome-mediated degradation. These results provide evidence for a new mechanism of transcriptional repression caused by doxorubicin in which the selective degradation of p300 results in reduced p300-dependent transcription, including production of MEF2C mRNA.
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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.