On the cutting edge: protease-based methods for sensing and controlling cell biology

Sequence-specific proteases have proven to be versatile building blocks for tools that report or control cellular function. Reporting methods link protease activity to biochemical signals, whereas control methods rely on engineering proteases to respond to exogenous inputs such as light or chemicals. In turn, proteases have inherent control abilities, as their native functions are to release, activate or destroy proteins by cleavage, with the irreversibility of proteolysis allowing sustained downstream effects. As a result, protease-based synthetic circuits have been created for diverse uses such as reporting cellular signaling, tuning protein expression, controlling viral replication and detecting cancer states. Here, we comprehensively review the development and application of protease-based methods for reporting and controlling cellular function in eukaryotes. This Review focuses on protease-based tools for sensing and controlling protein function in cell biology.