Publications
Read the highlights of our new work below or check out the full bibliography on Pubmed or Google Scholar
This study focused on the role of ISG15-modification in Listeria monocytogenes and Vaccinia virus spread. We found that Arp2, Arp3, and ArpC5 are modified by ISG15 following infection in the liver. ISGylation of proteins in the actin filament slows comet tail nucleation but paradoxically too much ISGylation allows Listeria to spread farther since bacteria can divide while attached to two stable actin filaments. ISG15-modification of actin filaments has implications for cell motility, barrier integrity, and cancer.
In a collaborative effort with the Impens laboratory at VIB in Ghent, the Radoshevich lab identified that the giant E3 ligase RNF213 colocalizes with the surface of cytosolic Listeria monocytogenes. RNF213 is mutated in Moya moya disease and is one of the most ISGylated proteins following Listeria infection. Our work suggests that RNF213 can modify the bacterial surface with ubiquitin, though the target of modification remains to be determined.
The Radoshevich laboratory's first independent paper which employed LC-MS/MS based proteomics to maps sites of ISGylation following Listeria monocytogenes infection in the liver. We leveraged Isg15-/- mice to identify the strict ubiquitylome and by extension the bone fide ISGylome. We found that ISG15 modifies enzymes at catalytic sites and dimerization domains of proteins. Furthermore, we showed that ISGylation upregulates autophagy through modification of mTOR.
Review of key findings in Listeria monocytogenes pathogenesis spanning lessons learned from clinical strains, new modes of regulation of virulence, and characterization of new classes of virulence factors.