文献类型：期刊文献

英文题名：An Endoplasmic Reticulum (ER)-Targeting DNA Nanodevice for Autophagy-Dependent Degradation of Proteins in Membrane-Bound Organelles

作者：Liu, Caixia X.[1];Wang, Bin[1];Zhu, Weiping P.[1,3];Xu, Yufang F.[1];Yang, Yangyang Y.[1];Qian, Xuhong H.[1,2]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Sch Pharm, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Me, 130 Mei Long Rd, Shanghai 200237, Peoples R China

年份：2022

卷号：61

期号：38

外文期刊名：ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

收录：;EI(收录号：20223212553034);WOS:【SCI-EXPANDED(收录号:WOS:000837471900001)】；

基金：This work was supported by the National Natural Science Foundation of China (Grant No. 31600802), the Research Funds of Happiness Flower ECNU (2020JK2103), Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism and Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：Autophagy; DNA Nanostructure; Organelle Targeting; Protein Degradation

摘要：Targeted protein degradation via proteasomal and lysosomal pathways is a promising therapeutic approach, and proteins in cytoplasm or on the cell membrane can be easily contacted and have become the major targets. However, degradation of disease-related proteins that exist in membrane-bound organelles (MBO) such as the endoplasmic reticulum (ER) remains unsolved due to the membrane limits. Here we describe a DNA nanodevice that shows ER targeting capacity and undergoes new intracellular degradation via the autophagy-dependent pathway. Then the DNA nanostructure functionalized with specific ligands is used to selectively catch ER-localized proteins and then transport them to the lysosome for degradation. Through this technique, the degradation of both exogenous ER-resident protein (ER-eGFP) and endogenous overexpressed molecular chaperone (glucose-regulated protein 78) in cancer cells has been successfully executed with high efficiency.