Simulating androgen receptor selection in designer yeast

doi:10.1016/j.synbio.2022.07.005

	Simulating androgen receptor selection in designer yeast
	Zhang, Haoran 5,6,7; Zhang, Lu 5,6,7; Xu, Yipeng 4; Chen, Shaoyong 2,3; Ma, Zhenyi 1,7; Yao, Mingdong 5,6,7; Li, Fangyin 4; Li, Bo 5,6,7; Yuan, Yingjin 5,6,7
刊名	SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
	2022-12-01
卷号	7
关键词	Androgen receptor mutations Androgen receptor antagonists Prostate cancer Saccharomyces cerevisiae
ISSN号	2405-805X
DOI	10.1016/j.synbio.2022.07.005
通讯作者	Yuan, Yingjin(yjyuan@tju.edu.cn)
英文摘要	Androgen receptor (AR) mutation is closely associated with prostate cancer (PCa) and is one of the mechanisms of resistance to PCa therapies such as AR antagonists. Although sequencing technologies like next-generation sequencing (NGS) contributes to the high-throughput and precise detection of AR mutations carried by PCa patients, the lack of interpretations of these clinical genetic variants has still been a roadblock for PCa-targeted precision medicine. Here, we established a designer yeast reporter assay to simulate natural androgen receptor (AR) selection using AR antagonists. Yeast HIS3 gene transactivation was associated with the ligand-induced recruitment of steroid receptor coactivator-1 (SRC-1) by AR mutants, where yeast growth in histidine-free me-dium was determined as the outcome. This assay is applicable to determine a wide range of clinical AR mutants including those with loss of function relating to androgen insensitivity syndrome (AIS), and those associated with PCa conferring resistance to AR antagonists such as enzalutamide (ENZ), bicalutamide (BIC), and cyproterone acetate (CPA). One clinical AR mutant previously reported to confer ENZ-resistance, F877L, was found to confer partial resistance to CPA as well using designer yeast. Our simple and efficient assay can enable precise one-pot screening of AR mutants, providing a reference for tailored medicine.
资助项目	National Natural Science Foundation of China[21621004] ; National Natural Science Foundation of China[31861143017]
WOS关键词	RESISTANT PROSTATE-CANCER ; STRUCTURAL BASIS ; BINDING DOMAIN ; CELL-GROWTH ; GENE ; MECHANISMS ; ENZALUTAMIDE ; ANTIANDROGEN ; BICALUTAMIDE ; MUTATIONS
WOS研究方向	Biotechnology & Applied Microbiology
语种	英语
出版者	KEAI PUBLISHING LTD
WOS记录号	WOS:000848339100001
资助机构	National Natural Science Foundation of China
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/131926]
专题	中国科学院合肥物质科学研究院
通讯作者	Yuan, Yingjin
作者单位	1.Tianjin Med Univ, Sch Basic Med Sci, Tianjin 300070, Peoples R China 2.Harvard Med Sch, Boston, MA 02215 USA 3.Beth Israel Deaconess Med Ctr, Dept Med, Hematol Oncol Div, Boston, MA 02215 USA 4.Univ Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp, Dept Urol, Hangzhou, Peoples R China 5.Tianjin Univ, Sch Chem Engn & Technol, Tianjin 300072, Peoples R China 6.Tianjin Univ, Key Lab Syst Bioengn, Minist Educ, Tianjin 300072, Peoples R China 7.Tianjin Univ, Frontier Sci Ctr Synthet Biol, Tianjin 300072, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Haoran,Zhang, Lu,Xu, Yipeng,et al. Simulating androgen receptor selection in designer yeast[J]. SYNTHETIC AND SYSTEMS BIOTECHNOLOGY,2022,7.
APA	Zhang, Haoran.,Zhang, Lu.,Xu, Yipeng.,Chen, Shaoyong.,Ma, Zhenyi.,...&Yuan, Yingjin.(2022).Simulating androgen receptor selection in designer yeast.SYNTHETIC AND SYSTEMS BIOTECHNOLOGY,7.
MLA	Zhang, Haoran,et al."Simulating androgen receptor selection in designer yeast".SYNTHETIC AND SYSTEMS BIOTECHNOLOGY 7(2022).