ArticleThe Journal of biological chemistry2016
HDAC8 Inhibition Blocks SMC3 Deacetylation and Delays Cell Cycle Progression without Affecting Cohesin-dependent Transcription in MCF7 Cancer Cells.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 59 citations in OpenAlex.
- Research progress on lysine acetylation (Review).International journal of molecular medicine · 2026Review
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Targeted HDAC8 inhibition with non-hydroxamate [1,2,4]triazolo[4,3-a] quinoline compounds.Scientific reports · 2026Article
- Differential effects of HDAC8 targeting on Foxp3+ Tregs and effector T cells promote antitumor immunity.JCI insight · 2026Article
- Unveiling the role of histone deacetylases in neurological diseases: focus on epilepsy.Biomarker research · 2024Review
- ZNF521 promotes acute myeloid leukemogenesis by suppressing the expression and acetylation of SMC3.Heliyon · 2024Article
- MicroRNA-mediated epigenetic regulation of HDAC8 and HDAC6: Functional significance in cervical cancer.Non-coding RNA research · 2024Article
- Reversible acetylation of HDAC8 regulates cell cycle.EMBO reports · 2024Article
- HDAC8-mediated inhibition of EP300 drives a transcriptional state that increases melanoma brain metastasis.Nature communications · 2023Article
- Targeting Histone Deacetylases 6 in Dual-Target Therapy of Cancer.Pharmaceutics · 2023Review
- Mechanistic Insights into the Anti-Proliferative Action of Gut Microbial Metabolites against Breast Adenocarcinoma Cells.International journal of molecular sciences · 2023Article
- HDAC8 Deacetylates HIF-1α and Enhances Its Protein Stability to Promote Tumor Growth and Migration in Melanoma.Cancers · 2023Article
- Regulation of the mitotic chromosome folding machines.The Biochemical journal · 2022Article
- Pathological Role of HDAC8: Cancer and Beyond.Cells · 2022Review
- Methionine 274 Is Not the Determining Factor for Selective Inhibition of Histone Deacetylase 8 (HDAC8) by L-Shaped Inhibitors.International journal of molecular sciences · 2022Article
- A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors.International journal of molecular sciences · 2022Review
- Review
- Validation of HDAC8 Inhibitors as Drug Discovery Starting Points to Treat Acute Kidney Injury.ACS pharmacology & translational science · 2022Article
- HDAC8 suppresses the epithelial phenotype and promotes EMT in chemotherapy-treated basal-like breast cancer.Clinical epigenetics · 2022Article
- Inhibitors of class I HDACs and of FLT3 combine synergistically against leukemia cells with mutant FLT3.Archives of toxicology · 2022Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cohesin, a multi-subunit protein complex involved in chromosome organization, is frequently mutated or aberrantly expressed in cancer. Multiple functions of cohesin, including cell division and gene expression, highlight its potential as a novel therapeutic target. The SMC3 subunit of cohesin is acetylated (ac) during S phase to establish cohesion between replicated chromosomes. Following anaphase, ac-SMC3 is deacetylated by HDAC8. Reversal of SMC3 acetylation is imperative for recycling cohesin so that it can be reloaded in interphase for both non-mitotic and mitotic functions. We blocked deacetylation of ac-SMC3 using an HDAC8-specific inhibitor PCI-34051 in MCF7 breast cancer cells, and examined the effects on transcription of cohesin-dependent genes that respond to estrogen. HDAC8 inhibition led to accumulation of ac-SMC3 as expected, but surprisingly, had no influence on the transcription of estrogen-responsive genes that are altered by siRNA targeting of RAD21 or SMC3. Knockdown of RAD21 altered estrogen receptor α (ER) recruitment at SOX4 and IL20, and affected transcription of these genes, while HDAC8 inhibition did not. Rather, inhibition of HDAC8 delayed cell cycle progression, suppressed proliferation and induced apoptosis in a concentration-dependent manner. We conclude that HDAC8 inhibition does not change the estrogen-specific transcriptional role of cohesin in MCF7 cells, but instead, compromises cell cycle progression and cell survival. Our results argue that candidate inhibitors of cohesin function may differ in their effects depending on the cellular genotype and should be thoroughly tested for predicted effects on cohesin's mechanistic roles.
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