Switching off protein production

Abstract

Protein Design Controlling protein production is desirable, but current methods are complex, inefficient, difficult to generalize, or not quickly reversible. Chung et al. describe a small-molecule–assisted shutoff (SMASh) tag that is genetically added to a target protein and allows reversible shutoff of various proteins in multiple cell types. The tag includes a site that is cut by a protease and a degron sequence that targets the protein for rapid destruction. Active protease cuts the tag from newly synthesized protein so that it does not disrupt protein function. However, inhibiting the protease with a clinically approved drug protects the tag, and the degron sequence causes the protein to be rapidly degraded. Stopping the drug restores protein production. Nat. Chem. Biol 10.1038/nchembio.1869 (2015).