A method to regulate protein function in living cells using synthetic small molecules

Nowadays, a lot of techniques for studies of gene expression and function are at DNA or mRNA level relying on a major strategy of perturbing a target gene expression and observing the change of phenotype. However, techniques that can regulate target proteins directly at protein level are required because of their higher efficiency. A rapid and reversible technique for protein function regulation in living cells is developed recently. It can change the stability of a target protein by expressing fused to mutated human FKBP12, a destabilizing domain, which can lead to degradation of the entire protein. The stability of the fusion protein can be control by attendance of a synthetic small molecule, Shld1, which can bind to FKBP12 and stop the degradation. This regulation is dose-depended and reversible. Therefore, predictable change of phenotype can be achieved by control the concentration of Shld1. In addition, this technique can be widely used in common cells lines to regulate various proteins.

Hu Lingbo
41943904