ArticleCell death & disease2017
Loss of GCN5 leads to increased neuronal apoptosis by upregulating E2F1- and Egr-1-dependent BH3-only protein Bim.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- Mitochondrial Dynamics-Related Gene Regulation by Epigenetic Suppression of GCN5 Exerts Neuroprotective Effects in Rotenone-Induced Parkinson's Disease Model.Molecular neurobiology · 2026Article
- Exploration of biomarkers associated with histone lactylation modification in spinal cord injury.Frontiers in genetics · 2025Article
- Article
- GCN5 mediates DNA-PKcs crotonylation for DNA double-strand break repair and determining cancer radiosensitivity.British journal of cancer · 2024Article
- Targeting the E2F1/Rb/HDAC1 axis with the small molecule HR488B effectively inhibits colorectal cancer growth.Cell death & disease · 2023Article
- Acetylation State of Lysine 14 of Histone H3.3 Affects Mutant Huntingtin Induced Pathogenesis.International journal of molecular sciences · 2022Article
- α-Synuclein upregulates bim-mediated apoptosis by negatively regulating endogenous GCN5.Aging · 2022Article
- MiR-106b-5p Attenuates Neuropathic Pain by Regulating the P2X4 Receptor in the Spinal Cord in Mice.Journal of molecular neuroscience : MN · 2022Article
- Epigenetic histone acetylation modulating prenatal Poly I:C induced neuroinflammation in the prefrontal cortex of rats: a study in a maternal immune activation model.Frontiers in cellular neuroscience · 2022Article
- Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan.Antioxidants (Basel, Switzerland) · 2021Review
- GCN5 acetyltransferase in cellular energetic and metabolic processes.Biochimica et biophysica acta. Gene regulatory mechanisms · 2021Review
- The Ageing Brain: Molecular and Cellular Basis of Neurodegeneration.Frontiers in cell and developmental biology · 2021Review
- Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid Suppresses Human Adenovirus Gene Expression and Replication.Journal of virology · 2019Article
- Effects of Prolonged Dietary Curcumin Exposure on Skeletal Muscle Biochemical and Functional Responses of Aged Male Rats.International journal of molecular sciences · 2019Article
- Drugs modulating stochastic gene expression affect the erythroid differentiation process.PloS one · 2019Article
- Inhibition of HDAC4 Attenuated JNK/c-Jun-Dependent Neuronal Apoptosis and Early Brain Injury Following Subarachnoid Hemorrhage by Transcriptionally Suppressing MKK7.Frontiers in cellular neuroscience · 2019Article
- GCN5 inhibition prevents IL-6-induced prostate cancer metastases through PI3K/PTEN/Akt signaling by inactivating Egr-1.Bioscience reports · 2018Article
- Article
- The Epigenetic Factor Landscape of Developing Neocortex Is Regulated by Transcription Factors Pax6→ Tbr2→ Tbr1.Frontiers in neuroscience · 2018Article
- NLRP3 inflammasome activation contributes to VSMC phenotypic transformation and proliferation in hypertension.Cell death & disease · 2017Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular acetylation homeostasis is a kinetic balance precisely controlled by histone acetyl-transferase (HAT) and histone deacetylase (HDAC) activities. The loss of the counterbalancing function of basal HAT activity alters the precious HAT:HDAC balance towards enhanced histone deacetylation, resulting in a loss of acetylation homeostasis, which is closely associated with neuronal apoptosis. However, the critical HAT member whose activity loss contributes to neuronal apoptosis remains to be identified. In this study, we found that inactivation of GCN5 by either pharmacological inhibitors, such as CPTH2 and MB-3, or by inactivation with siRNAs leads to a typical apoptosis in cultured cerebellar granule neurons. Mechanistically, the BH3-only protein Bim is transcriptionally upregulated by activated Egr-1 and E2F1 and mediates apoptosis following GCN5 inhibition. Furthermore, in the activity withdrawal- or glutamate-evoked neuronal apoptosis models, GCN5 loses its activity, in contrast to Bim induction. Adenovirus-mediated overexpression of GCN5 suppresses Bim induction and apoptosis. Interestingly, the loss of GCN5 activity and the induction of Egr-1, E2F1 and Bim are involved in the early brain injury (EBI) following subarachnoid haemorrhage (SAH) in rats. HDAC inhibition not only significantly rescues Bim expression and apoptosis induced by either potassium deprivation or GCN5 inactivation but also ameliorates these events and EBI in SAH rats. Taken together, our results highlight a new mechanism by which the loss of GCN5 activity promotes neuronal apoptosis through the transcriptional upregulation of Bim, which is probably a critical event in triggering neuronal death when cellular acetylation homeostasis is impaired.
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