ArticleThe Journal of steroid biochemistry and molecular biology2014
The N-terminal domain of the androgen receptor drives its nuclear localization in castration-resistant prostate cancer cells.
Article in The Journal of steroid biochemistry and molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Androgen receptor nucleocytoplasmic trafficking - A one-way journey.Molecular and cellular endocrinology · 2023Review
- The evolution and polymorphism of mono-amino acid repeats in androgen receptor and their regulatory role in health and disease.Frontiers in medicine · 2022Review
- Anti-Androgen Receptor Therapies in Prostate Cancer: A Brief Update and Perspective.Frontiers in oncology · 2022Review
- The classical and updated models of androgen receptor nucleocytoplasmic trafficking.American journal of clinical and experimental urology · 2021Review
- A new compound targets the AF-1 of androgen receptor and decreases its activity and protein levels in prostate cancer cells.American journal of cancer research · 2020Article
- Hsp70 Binds to the Androgen Receptor N-terminal Domain and Modulates the Receptor Function in Prostate Cancer Cells.Molecular cancer therapeutics · 2019Article
- Inhibition of Androgen Receptor Nuclear Localization and Castration-Resistant Prostate Tumor Growth by Pyrroloimidazole-based Small Molecules.Molecular cancer therapeutics · 2017Article
- Development and Implementation of a High-Throughput High-Content Screening Assay to Identify Inhibitors of Androgen Receptor Nuclear Localization in Castration-Resistant Prostate Cancer Cells.Assay and drug development technologies · 2016Article
- Splicing Factor Prp8 Interacts With NES(AR) and Regulates Androgen Receptor in Prostate Cancer Cells.Molecular endocrinology (Baltimore, Md.) · 2015Article
- A sting in the tail: the N-terminal domain of the androgen receptor as a drug target.Asian journal of andrologyReview
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Androgen-independent nuclear localization is required for androgen receptor (AR) transactivation in castration-resistant prostate cancer (CRPC) and should be a key step leading to castration resistance. However, mechanism(s) leading to androgen-independent AR nuclear localization are poorly understood. Since the N-terminal domain (NTD) of AR plays a role in transactivation under androgen-depleted conditions, we investigated the role of the NTD in AR nuclear localization in CRPC. Deletion mutagenesis was used to identify amino acid sequences in the NTD essential for its androgen-independent nuclear localization in C4-2, a widely used CRPC cell line. Deletion mutants of AR tagged with green fluorescent protein (GFP) at the 5'-end were generated and their signal distribution was investigated in C4-2 cells by fluorescent microscopy. Our results showed that the region of a.a. 294-556 was required for androgen-independent AR nuclear localization whereas a.a. 1-293 mediates Hsp90 regulation of AR nuclear localization in CRPC cells. Although the region of a.a. 294-556 does not contain a nuclear import signal, it was able to enhance DHT-induced import of the ligand binding domain (LBD). Also, transactivation of the NTD could be uncoupled from its modulation of AR nuclear localization in C4-2 cells. These observations suggest an important role of the NTD in AR intracellular trafficking and androgen-independent AR nuclear localization in CRPC cells.
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