Cells need proteins to carry out various biological functions, usually tagged to determine/modify their cellular activity. Now, scientists from the University of Iowa, US, who studied proteins tagged ISG15, have developed a novel method to better understand the workings of the immune system.

The research began with a small protein called ubiquitin, which was first discovered as a label to tag a protein for degradation. While ISG15 has an ubiquitin-like modification, its exact sites of modification were unknown. The tool used to identify ubiquitin modification sites was thus used for the identification of ISG15 modification sites. As ISG15 is only expressed upon stresses such as a viral or bacterial infection, the livers of mice were analysed for ISG15 after being infected with Listeria.

Scientists from the university’s labs – of Professor Francis Impens and Professor Lilliana Radoshevich – explained that Listeria is an accessible food-borne bacterial pathogen that hides inside host cells and is most likely removed by the liver. Both labs then reported a first discovery of nearly a thousand ISG15 sites on more than four hundred protein targets during the Listeria infection.

Prof. Radoshevich said that ISG15 was found to target key regulators of autophagy, a process in response to a lack of nutrients in a cell,“It leads to the destruction of cellular components to generate energy and promote cell survival. Autophagy can also be used as an antibacterial strategy.”

The scientists hope future ISG15 studies would reveal antimicrobial pathways of our immune system that can be exploited to design new drugs.