LAUSR

Protein functions and cellular signaling pathways can be modulated by selectively degrading certain proteins. PROTACs, proteolysis-targeting chimeras, are molecules that recognize and bind both the protein of interest and E3 ubiquitin ligase — an enzyme that facilitates degradation of the target protein. These constructs have had considerable success, but finer control of their activity is desirable. Xue et al. have developed photo-caged (pc) PROTACs that are activated and released upon irradiation with light and can target proteins to induce desired phenotypes. The authors constructed pc-PROTACs using Brd4 protein — of interest in cancer therapy — as the target. Upon treatment, Brd4 degradation was induced successfully using photoactivation in both live Ramos cells and zebrafish embryos, with activity comparable to that of non-pc PROTACs. The added control could be helpful in both mechanistic studies and the design of localized treatment strategies.