ArticleThe EMBO journal2003
The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2.
Article in The EMBO journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 225 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
225 citing papers in PubMed, 1 synthesis or guideline pooled it, 525 citations in OpenAlex.
- COVID-19 outbreak: history, mechanism, transmission, structural studies and therapeutics.Infection · 2021Pooled it
- Molecular dissection of valproic acid effects in acute myeloid leukemia identifies predictive networks.Epigenetics · 2016Trial
- A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results.Medical oncology (Northwood, London, England) · 2011Trial
- Cigarette Smoke-Exposed Alveolar Epithelial Cell-Derived Exosomes Exacerbate Skeletal Muscle Dysfunction Through HDAC2 Signalling.Journal of cachexia, sarcopenia and muscle · 2026Article
- The Role of Glycan Structures in Modulating GM-CSF Bioactivity: Insights from Glycoengineering.bioRxiv : the preprint server for biology · 2026Article
- Impact of keto leucine and isoleucine on CHO cell central carbon metabolism and performance in fed-batch and steady-state perfusion.Frontiers in bioengineering and biotechnology · 2026Article
- Novel small molecules downregulate CDK1 expression and inhibit Wnt/β-catenin signaling in cutaneous squamous cell carcinoma by targeting its distinct tumor-specific cellular landscape.Experimental & molecular medicine · 2025Article
- Epigenetic Therapies in Endocrine-Related Cancers: Past Insights and Clinical Progress.Cancers · 2025Review
- A New Treatment Strategy for Lung Cancer With HDAC and Wnt/β-Catenin Pathway Inhibitors.IUBMB life · 2025Article
- Ubiquitin proteasome system (UPS): a crucial determinant of the epigenetic landscape in cancer.Epigenomics · 2025Review
- PJA2 Suppresses Colorectal Cancer Progression by Controlling HDAC2 Degradation and Stability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Loss of Notch dimerization perturbs intestinal homeostasis by a mechanism involving HDAC activity.PLoS genetics · 2024Article
- Fatty acids and epigenetics in health and diseases.Food science and biotechnology · 2024Review
- HAT and HDAC: Enzyme with Contradictory Action in Neurodegenerative Diseases.Molecular neurobiology · 2024Review
- Tissue engineering approaches for dental pulp regeneration: The development of novel bioactive materials using pharmacological epigenetic inhibitors.Bioactive materials · 2024Review
- Gliomagenesis, Epileptogenesis, and Remodeling of Neural Circuits: Relevance for Novel Treatment Strategies in Low- and High-Grade Gliomas.International journal of molecular sciences · 2024Review
- Epigenetic mechanisms differentially regulate blood pressure and renal dysfunction in male and female Npr1 haplotype mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- How does the Xist activator Rlim/Rnf12 regulate Xist expression?Biochemical Society transactions · 2024Review
- Valproic Acid Causes Redox-Regulated Post-Translational Protein Modifications That Are Dependent upon P19 Cellular Differentiation States.Antioxidants (Basel, Switzerland) · 2024Article
- Review
165 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone-modifying enzymes play essential roles in physiological and aberrant gene regulation. Since histone deacetylases (HDACs) are promising targets of cancer therapy, it is important to understand the mechanisms of HDAC regulation. Selective modulators of HDAC isoenzymes could serve as efficient and well-tolerated drugs. We show that HDAC2 undergoes basal turnover by the ubiquitin-proteasome pathway. Valproic acid (VPA), in addition to selectively inhibiting the catalytic activity of class I HDACs, induces proteasomal degradation of HDAC2, in contrast to other inhibitors such as trichostatin A (TSA). Basal and VPA-induced HDAC2 turnover critically depend on the E2 ubiquitin conjugase Ubc8 and the E3 ubiquitin ligase RLIM. Ubc8 gene expression is induced by both VPA and TSA, whereas only TSA simultaneously reduces RLIM protein levels and therefore fails to induce HDAC2 degradation. Thus, poly-ubiquitination and proteasomal degradation provide an isoenzyme-selective mechanism for downregulation of HDAC2.
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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.