Celastrol recruits UBE3A to recognize and degrade the DNA binding domain of steroid receptors
文献类型:期刊论文
作者 | Tan, Qilong1; Liu, Ziqun1; Gao, Xiaobo2,3; Wang, Yibo5,6; Qiu, Xuefeng7; Chen, Jiahui8; Liang, Liuchun8; Guo, Hongqian7; Huang, Shengsong8; Wu, Denglong8 |
刊名 | ONCOGENE |
出版日期 | 2022-10-14 |
卷号 | 41期号:42页码:4754-4767 |
ISSN号 | 0950-9232 |
DOI | 10.1038/s41388-022-02467-8 |
文献子类 | Article |
英文摘要 | Strategies to degrade steroid receptors and their alternative splicing isoforms are critical for disease management. Here we report that celastrol recruited the ubiquitin ligase UBE3A and degraded androgen receptor (AR), AR-v7, and glucocorticoid receptor (GR) to suppress prostate cancer development. UBE3A was not an optimal endogenous AR ubiquitin ligase in mice and patients, but celastrol promoted the interaction between UBE3A and AR. Multiple domains of AR, including the DNA binding domain (DBD), were implicated into the UBE3A-AR interaction. Sharing a conserved DBD, GR, AR-v7, and other steroid receptors were recognized and degraded by UBE3A after celastrol treatment. Thus, celastrol suppressed prostate cancer cell proliferation more potently than enzalutamide. Modifying the carboxyl group of celastrol improved its anti-tumor activity. Together, our findings revealed that celastrol might be a potential molecular glue to enhance the interaction between UBE3A and steroid receptors to degrade multiple steroid receptors and splicing isoforms in prostate cancer, paving a way for further drug optimization and disease treatment. |
WOS关键词 | UBIQUITIN-PROTEIN LIGASE ; PROSTATE-CANCER ; ANDROGEN-RECEPTOR ; E6-ASSOCIATED PROTEIN ; E6-AP ; ENZALUTAMIDE ; RESISTANCE ; COACTIVATOR ; EXPRESSION ; MUTATIONS |
WOS研究方向 | Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity |
语种 | 英语 |
出版者 | SPRINGERNATURE |
WOS记录号 | WOS:000854052300001 |
源URL | [http://119.78.100.183/handle/2S10ELR8/309304] |
专题 | 新药研究国家重点实验室 |
通讯作者 | Zhou, Bing; Hu, Ronggui; Li, Zhenfei |
作者单位 | 1.Univ Chinese Acad Sci, State Key Lab Cell Biol, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol,Chinese Acad Sc, 320 Yueyang Rd, Shanghai 200031, Peoples R China; 2.Fudan Univ, State Key Lab Med Neurobiol, Inst Translat Brain Res, Shanghai 200032, Peoples R China; 3.Fudan Univ, MOE Frontiers Ctr Brain Sci, Shanghai 200032, Peoples R China; 4.Univ Chinese Acad Sci, Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol,State Key Lab M, 320 Yueyang Rd, Shanghai 200031, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 6.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China; 7.Nanjing Univ, Med Sch, Affiliated Drum Tower Hosp, Dept Urol, Nanjing 210008, Peoples R China; 8.Tongji Univ, Tongji Hosp, Sch Med, Dept Urol, Shanghai 200065, Peoples R China |
推荐引用方式 GB/T 7714 | Tan, Qilong,Liu, Ziqun,Gao, Xiaobo,et al. Celastrol recruits UBE3A to recognize and degrade the DNA binding domain of steroid receptors[J]. ONCOGENE,2022,41(42):4754-4767. |
APA | Tan, Qilong.,Liu, Ziqun.,Gao, Xiaobo.,Wang, Yibo.,Qiu, Xuefeng.,...&Li, Zhenfei.(2022).Celastrol recruits UBE3A to recognize and degrade the DNA binding domain of steroid receptors.ONCOGENE,41(42),4754-4767. |
MLA | Tan, Qilong,et al."Celastrol recruits UBE3A to recognize and degrade the DNA binding domain of steroid receptors".ONCOGENE 41.42(2022):4754-4767. |
入库方式: OAI收割
来源:上海药物研究所
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