Detection of protein-protein interactions in live cells and animals with split firefly luciferase protein fragment complementation

Protein fragment complementation has emerged as a powerful tool for measuring protein-protein interactions in the context of live cells. The adaptation of this strategy for use with firefly luciferase now allows for the non-invasive, quantitative, real-time readout of protein interactions in lysates, live cells, and whole animals. Bioluminescence provides a robust imaging modality due to its extremely low background signal and large dynamic range. The split luciferase fusion constructs described here are inducible by addition of ligands, small molecules or drugs, in this example, rapamycin, and have been shown to work in vivo.