Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32948771.
- Also identified by DOI 10.1038/s41467-020-18377-w and PMC identifier 7501296.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Chemical biology strategies for directly perturbing protein homeostasis including the degradation tag (dTAG) system provide temporal advantages over genetic approaches and improved selectivity over small molecule inhibitors. We describe dTAG<sup>V</sup>-1, an exclusively selective VHL-recruiting dTAG molecule, to rapidly degrade FKBP12<sup>F36V</sup>-tagged proteins. dTAG<sup>V</sup>-1 overcomes a limitation of previously reported CRBN-recruiting dTAG molecules to degrade recalcitrant oncogenes, supports combination degrader studies and facilitates investigations of protein function in cells and mice.
Medical subject headings
- Peptide Hydrolases
- Proteins
- Von Hippel-Lindau Tumor Suppressor Protein