摘要
Treatment with individual anti-androgens is associated with the development of hot-spot mutations in the androgen receptor (AR). Here, we found that anti-androgens-mt-ARs have similar binary structure to the 5α-dihydrotestosterone-wt-AR. Phage display revealed that these ARs bound to similar peptides, including BUD31, containing an Fxx(F/H/L/W/Y)Y motif cluster with Tyr in the +5 position. Structural analyses of the AR-LBD-BUD31 complex revealed formation of an extra hydrogen bond between the Tyr+5 residue of the peptide and the AR. Functional studies showed that BUD31-related peptides suppressed AR transactivation, interrupted AR N-C interaction, and suppressed AR-mediated cell growth. Combination of peptide screening and X-ray structure analysis may serve as a new strategy for developing anti-ARs that simultaneously suppress both wt and mutated AR function.
原文 | 英語 |
---|---|
頁(從 - 到) | 1575-1587 |
頁數 | 13 |
期刊 | Molecular Oncology |
卷 | 8 |
發行號 | 8 |
DOIs | |
出版狀態 | 已發佈 - 12月 1 2014 |
ASJC Scopus subject areas
- 分子醫學
- 腫瘤科
- 遺傳學
- 癌症研究