Strategies that selectively bind proteins of interest and target them to the intracellular protein recycling machinery for targeted protein degradation have recently emerged as powerful tools for undruggable targets in biomedical research and the pharmac
Strategies that selectively bind proteins of interest and target them to the intracellular protein recycling machinery for targeted protein degradation have recently emerged as powerful tools for undruggable targets in biomedical research and the pharmaceutical industry. However, targeting any new protein of...
Protein degradation is an essential function for all living cells1. Recently there has been a sizeable effort to engineer the degradation of target proteins for therapeutic benefit2,3. At the forefront of this newly emerging field are heterobifunctional molecules that bind to both a target protein ...
Subcellular protein localization regulates protein function and can be corrupted in cancers1 and neurodegenerative diseases2,3. The rewiring of localization to address disease-driving phenotypes would be an attractive targeted therapeutic approach. Molec
Synthesis and degradation of proteins maintain cellular metabolic integrity and proliferation. The proteasome, a multimeric protease complex, plays a key role in cellular protein regulation by degrading proteins, thus regulating many pathways.30, 31 The ubiquitin–proteasome system was initially discovered ...
By taking advantage of acute protein degradation systems, we first examined RNA Pol II subunit degron cells to ensure that they were similar to the wild-type mESCs in regard to gene expression, cell morphology, etc., and then carefully minimized the potential secondary effects. Poly(A) RNA-...
Hijacking the cellular protein degradation system offers unique opportunities for drug discovery, as exemplified by proteolysis-targeting chimeras. Despite their great promise for medical chemistry, so far, it has not been possible to reprogram the bacterial degradation machinery to interfere with microbial...
Proteolysis-targeting chimera (PROTAC) has been developed to be a useful technology for targeted protein degradation. A bifunctional PROTAC molecule consists of a ligand (mostly small-molecule inhibitor) of the protein of interest (POI) and a covalently
Targeted protein degradation reveals BET bromodomains as the cellular target of Hedgehog pathway inhibitor-1 Meropi Bagka, Hyeonyi Choi, Margaux Héritier, Hanna Schwaemmle, Quentin T. L. Pasquer, Simon M. G. Braun, Leonardo Scapozza, Yibo Wu & Sascha Hoogendoorn Nature Communicat...
Proteolysis-targeting chimeras (PROTACs) and related molecules that induce targeted protein degradation by the ubiquitin–proteasome system represent a new therapeutic modality and are the focus of great interest, owing to potential advantages over traditional occupancy-based inhibitors with respect to dosing...