ArticleCancer research2020
p300-Mediated Acetylation of Histone Demethylase JMJD1A Prevents Its Degradation by Ubiquitin Ligase STUB1 and Enhances Its Activity in Prostate Cancer.
Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 64 citations in OpenAlex.
- Zinc-dependent Zip7-MAZ-MYBL2 axis promotes prostate cancer metastasis.Communications biology · 2026Article
- Identification of A p300-SP1-BRD4 Transcriptional Axis as a Key Driver of AR Hyperactivation in Polycystic Ovarian Syndrome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The JMJD family histone demethylases: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- PDHA1-acetylation signaling suppresses cuproptosis to attenuate anti-androgen effect in prostate cancer.Cell death & disease · 2026Article
- Transcriptional and epigenetic reprogramming, lineage plasticity and therapy resistance in prostate cancer.Journal of the National Cancer Center · 2026Review
- p300: expanding beyond acetylation to mastermind lactylation-dependent tumorigenesis.Frontiers in cell and developmental biology · 2026Review
- BPTF regulates androgen receptor activity by enhancing chromatin accessibility and stabilizing the AR-FOXA1 interaction.Nature communications · 2025Article
- The STUB1-TPIT axis regulates the secretion of adrenocorticotrophic hormone in cushing disease.Journal of translational medicine · 2025Article
- Glucose-induced STUB1-GOT2 axis promotes aspartate synthesis and mitochondrial dysfunction in bladder cancer.Cell death & disease · 2025Article
- Loss of RNF41 promotes bladder cancer metastasis through increasing NUDC stability to enhance tubulin polymerization.Cell death & disease · 2025Article
- Acetylation: a new target for protein degradation in cancer.Trends in cancer · 2025Review
- Proteasome inhibition induces DNA methylation alteration by attenuating the synthesis of DNA methyltransferase 1 and 3B in colorectal cancer.Scientific reports · 2025Article
- The mechanism of histone modifications in regulating enzalutamide sensitivity in advanced prostate cancer.International journal of biological sciences · 2025Review
- Unleashing the power of peptides in prostate cancer immunotherapy: mechanism, facts and perspectives.Frontiers in pharmacology · 2025Review
- The Activation of p300 Enhances the Sensitivity of Pituitary Adenomas to Dopamine Agonist Treatment by Regulating the Transcription of DRD2.International journal of molecular sciences · 2024Article
- USP3 promotes DNA damage response and chemotherapy resistance through stabilizing and deubiquitinating SMARCA5 in prostate cancer.Cell death & disease · 2024Article
- KDM3A Ablation Activates Endogenous Retrovirus Expression to Stimulate Antitumor Immunity in Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Histone lysine methylation modifiers controlled by protein stability.Experimental & molecular medicine · 2024Review
- A noncanonical E3 ubiquitin ligase RNF41-mediated MYO1C stability promotes prostate cancer metastasis by inducing actin remodeling.Oncogene · 2024Article
- USP11 promotes prostate cancer progression by up-regulating AR and c-Myc activity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
The androgen receptor (AR) pathway plays a central role in the development of castration-resistant prostate cancer (CRPC). The histone demethylase JMJD1A has been shown to regulate activities of AR and c-Myc transcription factors and promote prostate cancer progression. Here, we report that JMJD1A protein stability is controlled by the ubiquitin ligase STUB1. High levels of JMJD1A were strongly correlated with low STUB1 levels in human CRPC specimens. STUB1 inhibited AR activity, AR-V7 levels, and prostate cancer cell growth partly through degradation of JMJD1A. Furthermore, the acetyltransferase p300 acetylated JMJD1A at lysine (K) 421, a modification that recruits the BET family member BRD4 to block JMJD1A degradation and promote JMJD1A recruitment to AR targets. Increased levels of both total and K421-acetylated JMJD1A were observed in prostate cancer cells as they developed resistance to the AR antagonist enzalutamide. Treatment of prostate cancer cells with either p300 or BET inhibitors destabilized JMJD1A, and enzalutamide-resistant prostate cancer cells were more sensitive than parental cells to these inhibitors. Together, our findings identify a critical role for acetylation of JMJD1A in regulating JMJD1A stability and AR activity in CRPC. These newly identified mechanisms controlling JMJD1A protein stability provide potential druggable targets to encourage the development of additional therapies for advanced prostate cancer. SIGNIFICANCE: Identification of mechanisms regulating JMJD1A protein stability reveals new strategies to destabilize JMJD1A and concomitantly inhibit AR activities as potential prostate cancer therapy.
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