Characterization of cereblon-dependent targeted protein degrader by visualizing the spatiotemporal ternary complex formation in cells.

ABSTRACT: Targeted protein degradation (TPD) through a proteasome-dependent pathway induced by heterofunctional small molecules is initiated by the formation of a ternary complex with recruited E3 ligases. This complex formation affects the degradation ability of TPD molecules, and thus we tested for visualization of the intracellular dynamics of ternary complex formation. In this study, we applied the fluorescent-based technology detecting protein-protein interaction (Fluoppi) system, in which detectable fluorescent foci are formed when ternary complex formation induced by TPD molecules occurs in cells. We show here that cells coexpressing BRD4 and cereblon (CRBN) tagged with the Fluoppi system formed detectable foci in both live and fixed cells only when treated with BRD4-targeting degraders utili

SUBMITTER: Kaji T 

PROVIDER: S-EPMC7033280 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature