文献类型：期刊文献

英文题名：A nanobody-based molecular toolkit for ubiquitin-proteasome system explores the main role of survivin subcellular localization

作者：Miao, Hui[1];Liu, Chang[1];Ouyang, Hao[2];Zhang, Peiwen[3];Liu, Yuping[3];Zhang, Chen[1];Deng, Changping[1];Fu, Yunhui[1];Niu, Jinping[1];Zheng, Wenyun[3];You, Fang[4];Yang, Yi[4];Ma, Xingyuan[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]Shanghai Univ Tradit Chinese Med, Yueyang Hosp Integrated Tradit Chinese & Western M, Dept Hepatol, Shanghai, Peoples R China;[3]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai, Peoples R China;[4]Natl Univ Singapore, Dept Chem & Biomol Engn, Singapore, Singapore

年份：2023

卷号：10

外文期刊名：FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY

收录：;EI(收录号：20230613556186);WOS:【SCI-EXPANDED(收录号:WOS:000924028300001)】；

基金：Funding 'This study was supported by the National Key Research and Development Project of China (2018YFA0902804) and the National Natural Science Foundation (31670944 and 81673345).

语种：英文

外文关键词：survivin subcellular function; nanobody targeted; TRIM21; apoptosis and cell cycle; anti-cancer

摘要：Targeted protein degradation is a powerful tool for determining the function of specific proteins nowadays. Survivin is the smallest member of the inhibitor of the apoptosis protein (IAP) family. It exists in the cytoplasm and nucleus of cells, but the exact function of survivin in different subcellular locations retained unclear updates due to the lack of effective and simple technical means. In this study, we created a novel nanoantibody-based molecular toolkit, namely, the ubiquitin-proteasome system (Nb4A-Fc-T2A-TRIM21), that can target to degrade survivin localized in cytoplasmic and cell nuclear by ubiquitinating, and by which to verify the potential roles of survivin subcellular localization. Also, the results showed that the cytoplasmic survivin mainly plays an anti-apoptotic function by directly or indirectly inhibiting the caspase pathway, and the nuclear survivin mainly promotes cell proliferation and participates in the regulation of the cell cycle. In addition, the Nb4A-Fc-T2A-TRIM21 system can degrade the endogenous survivin protein in a large amount by the ubiquitin-proteasome pathway, and the system can provide theoretical support for ubiquitination degradation targeting other endogenous proteins.