ArticleProceedings of the National Academy of Sciences of the United States of America2023
TRAF4-mediated nonproteolytic ubiquitination of androgen receptor promotes castration-resistant prostate cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Alterations in AR-FOXA1 signaling in prostate cancer progression and therapeutic resistance.Journal of the National Cancer Center · 2026Review
- A Hypoxia and Immune Escape-Related Gene Signature for the Diagnosis of Prostate Cancer: An Integrated Bioinformatics Study.International journal of medical sciences · 2026Article
- STARD4 suppresses tumorigenesis and attenuates enzalutamide resistance via lipid metabolic reprogramming and AR stabilization in prostate cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Post-Translational Modifications in Cilia and Ciliopathies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- HOXB13 in cancer development: molecular mechanisms and clinical implications.Frontiers of medicine · 2025Review
- TRAPT: a multi-stage fused deep learning framework for predicting transcriptional regulators based on large-scale epigenomic data.Nature communications · 2025Article
- Identification of E3 Ubiquitin Ligase Substrates Using Biotin Ligase-Based Proximity Labeling Approaches.Biomedicines · 2025Review
- Lnc-EST885 promotes hepatocellular carcinoma metastasis through PI3K / AKT pathway by interaction with TRAF4.Translational oncology · 2025Article
- The role of ubiquitination and deubiquitination in urological tumours.Frontiers in pharmacology · 2025Review
- Prognostic model of ubiquitination-related genes in ovarian cancer based on transcriptomic analysis and experimental validation.Frontiers in immunology · 2025Article
- USP33 facilitates the ovarian cancer progression via deubiquitinating and stabilizing CBX2.Oncogene · 2024Article
- Review
- TRAF4 regulates ubiquitination-modulated survivin turnover and confers radioresistance.International journal of biological sciences · 2024Article
Corrections and comments
- Commented on byUro-Science.2024
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Castration-resistant prostate cancer (CRPC) poses a major clinical challenge with the androgen receptor (AR) remaining to be a critical oncogenic player. Several lines of evidence indicate that AR induces a distinct transcriptional program after androgen deprivation in CRPCs. However, the mechanism triggering AR binding to a distinct set of genomic loci in CRPC and how it promotes CRPC development remain unclear. We demonstrate here that atypical ubiquitination of AR mediated by an E3 ubiquitin ligase TRAF4 plays an important role in this process. TRAF4 is highly expressed in CRPCs and promotes CRPC development. It mediates K27-linked ubiquitination at the C-terminal tail of AR and increases its association with the pioneer factor FOXA1. Consequently, AR binds to a distinct set of genomic loci enriched with FOXA1- and HOXB13-binding motifs to drive different transcriptional programs including an olfactory transduction pathway. Through the surprising upregulation of olfactory receptor gene transcription, TRAF4 increases intracellular cAMP levels and boosts E2F transcription factor activity to promote cell proliferation under androgen deprivation conditions. Altogether, these findings reveal a posttranslational mechanism driving AR-regulated transcriptional reprogramming to provide survival advantages for prostate cancer cells under castration conditions.
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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.