Membrane‐Bounded Intracellular E3 Ubiquitin Ligase‐Targeting Chimeras (MembTACs) for Targeted Membrane Protein Degradation
Abstract
AbstractTargeted protein degradation (TPD) represents a potent therapeutic strategy aimed at dismantling disease‐associated target proteins. PROTAC is the most widely developed technique for intracellular protein degradation, while its degradation ability on membrane proteins has been hindered by the need for complex synthetic processes and limited permeability. In this study, we developed the membrane‐bounded intracellular E3 ubiquitin ligase‐targeting chimeras (MembTACs) that simultaneously recruit intracellular E3 ubiquitin ligase and bind to the desired membrane proteins for targeted degradation of membrane proteins. We demonstrate that the MembTACs can effectively utilize intracellular E3 ubiquitin ligase to degrade the therapeutically relevant membrane proteins of EpCAM and Met via the proteasome pathway. We anticipate that the new platform will expand the range of PROTAC applications and provide a new dimension for targeted membrane protein degradation.
Article Details
Authors (7)
Mengwu Mo
MOE Key Laboratory of Spectrochemical Analysis and Instrumentation State Key Laboratory of Physical Chemistry of Solid Surfaces Key Laboratory for Chemical Biology of Fujian Province Department of Chemical Biology College of Chemistry and Chemical Engineering Xiamen University Xiamen China
Feiyu Wang
Huiming Zhang
Shanghai Center for Plant Stress Biology, Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences
Ying Zhang
Chaoyong Yang
State Key Laboratory of Physical Chemistry of Solid Surfaces, Key Laboratory for Chemical Biology of Fujian Province, The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory of Vaccines for Infectious Diseases, Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, School of Life Sciences, Faculty of Medicine and Life Sciences
Jinbiao Shang
Zhi Zhu
State Key Laboratory of Physical Chemistry of Solid Surfaces, Key Laboratory for Chemical Biology of Fujian Province, The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory of Vaccines for Infectious Diseases, Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, School of Life Sciences, Faculty of Medicine and Life Sciences