Chemical inducers of targeted protein degradation

Abstract

The functions of many cellular proteins have been elucidated by selective gene inactivation and subsequent phenotypic analysis. For example, genetic mutations, gene knock-out generation, and the use of RNA interference to target mRNA for degradation can all result in decreased production of a specific protein, yielding informative cellular phenotypes. However, these techniques each have certain inherent limitations. This minireview focuses on the recent development of new approaches to study protein function at the post-translational level, namely chemical induction of targeted protein degradation.

FIGURE 1.

Chemical means of controlling protein function. A, direct localization to the proteasome; B, the destabilizing domain approach; C, PROTAC-mediated degradation; D, SURF technology. Ub, ubiquitin.