Biology Seminar - Nov. 13 at 11 a.m.

Biology Seminar
Tuesday, November 13, 2018
Noyce Science Center, Room 2022
11 a.m.

Dr. Lilliana Radoshevich '04

Assistant Professor of Microbiology and Immunology
University of Iowa

will be presenting:

Linking ISG15 to Cellular Stress Responses: Lessons from Listeria infection

ISG15 is an interferon-stimulated, ubiquitin-like protein, with anti-viral activity, however its role during bacterial infection had not been addressed. We previously found that ISG15 restricts Listeria infection both in vitro and in vivo and identified ISGylated proteins that could be responsible for the protective effect. Strikingly, infection or overexpression of ISG15 leads to ISGylation of ER and Golgi proteins, which correlates with increased secretion of cytokines known to counteract infection. More recently, we endeavored to map the in vivo ISGylome following Listeria infection to mechanistically understand the function of this pathway in host defense. To do so we combined a genetic approach employing a murine model of hyper-ISGylation with quantitative proteomics of immunoenriched endogenous ISG15 modification sites. In addition, our approach mapped the endogenous ubiquitylome following infection with Listeria in vivo including the identification of several modified bacterial proteins. Interestingly, we detected ISG15 sites in a number of ER and Golgi proteins, which we had previously shown to be ISG15 targets in vitro, as well as proteins known to control cellular stress responses such as ER stress and autophagy. Taken together, this work will open the door to understanding mechanisms of action of an understudied ubiquitin-like protein.