Activate On Command

Controlling protein function in mammalian cells could get a little easier. Researchers at Harvard University describe a way to turn on proteins with laboratory-evolved self-splicing protein domains called inteins.

Chemist David R. Liu, biologist Andrew P. McMahon, and coworkers use an intein evolved in yeast that only works when it binds the small molecule 4-hydroxytamoxifen (4-HT), at which point the intein splices itself out of the protein, reconnects the two halves, and thereby activates the protein.

The researchers use the intein to control the function of green fluorescent protein and two protein transcription factors in the hedgehog signaling pathway, which is involved in development (J. Am. Chem. Soc., published online June 16, dx.doi.org/10.1021/ja062980e). In addition, inserting the intein in one of the transcription factors makes 4-HT trigger the differentiation of mouse embryonic cells to osteoblasts, a type of bone cell.

So far, the researchers have shown that the intein works in seven unrelated yeast and mammalian proteins, suggesting that the method may be a general tool for studying protein function.