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A Genomic Approach To Assessing The Fkbp52-Regulated Androgen Receptor Cistrome And Transcriptome, Nina Raquelle Ortiz

Open Access Theses & Dissertations

Androgen receptor (AR)-regulated genes contribute to the initiation and progression of prostate cancer. Receptor signaling persists and plays a pivotal role in late-stages of the disease, for which there is currently no treatment. Thus, there is a need to understand the mechanisms regulating AR function as a means to identify drug targets for potential therapeutics. The FKBP52 cochaperone has emerged in recent years as a regulator of AR activity that is functionally linked in the AR signaling pathway. FKBP52 is a known positive regulator of AR and believed to interact with AR at its binding function 3 surface (BF3), a …

Identification And Characterization Of Small Molecules Targeting Fkbp52 As A Novel Treatment For Prostate Cancer, Naihsuan C. Guy

Open Access Theses & Dissertations

Prostate cancer (PCa) is one of the most commonly diagnosed diseases and the second leading cause of cancer deaths among men worldwide. Its growth is dependent upon androgen receptor (AR) signaling and the mainstay for treatment is hormone-ablation therapy using antiandrogens and/or androgen-deprivation therapies (ADT). Treatment of PCa with antiandrogens and/or ADT are initially effective; they act to repress the AR by directly competing with androgens for the ligand binding domain (LBD) and prevent activation of the receptor resulting in tumor regression. Unfortunately, the resistance to these treatments invariably emerges and results in a much more aggressive form of tumor …

A Novel Fkbp52/Β-Catenin Complex Specifically Regulates Androgen Receptor Activity, Cheryl Lynne Storer

Open Access Theses & Dissertations

The androgen receptor complex plays an essential role in prostate cancer progression due to exploitation of the androgen receptor (AR) as a transcription factor. The final stage of the receptor complex consists of a dimerized receptor, a dimeric heat shock protein (Hsp90), the cochaperone p23, and an immunophilin. Hormone-dependent prostate cancer progresses due to key interactions between the androgen receptor complex and its ligand α dihydrotestosterone (DHT). While current treatments focus on blocking the androgen receptor-ligand interactions, these therapies are no longer effective in advanced stage, hormone-refractory prostate cancer (HRPC).

Therefore, we have been interested in targeting other members of …

Identification And Characterization Of Fkbp52-Specific Inhibitors For The Treatment Of Prostate Cancer, Johanny Tonos De Leon

Open Access Theses & Dissertations

Steroid hormone receptors require the ordered assembly of various chaperone and cochaperone proteins in order to reach a functional state. The final stage in the receptor maturation process requires the formation of a mutimeric complex consisting of Hsp90 dimer, p23, and one of several large immunophilins. Studies conducted previously demonstrated that the large immunophilin FKBP52 acts to potentiate glucocorticoid, androgen, and progesterone receptor signaling pathways. The aim of these studies was to identify and characterize FKBP52-specific inhibitors that would not only serve as tools for the pharmacological analysis of FKBP52-receptor interactions, but may also lead to novel drugs with significant …