The dTAG system for immediate and target-specific protein degradation.

ABSTRACT: Dissection of complex biological systems requires target-specific control of the function or abundance of proteins. Genetic perturbations are limited by off-target effects, multicomponent complexity, and irreversibility. Most limiting is the requisite delay between modulation to experimental measurement. To enable the immediate and selective control of single protein abundance, we created a chemical biology system that leverages the potency of cell-permeable heterobifunctional degraders. The dTAG system pairs a novel degrader of FKBP12^F36V with expression of FKBP12^F36V in-frame with a protein of interest. By transgene expression or CRISPR-mediated locus-specific knock-in, we exemplify a generalizable strategy to study the immediate consequence of protein loss. Using d

SUBMITTER: Nabet B 

PROVIDER: S-EPMC6295913 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature