Jon Huibregtse, University of Texas - Austin
Host: Yuxin Mao
Double Duty: The ISG15 Ubiquitin-like Protein in Innate Immune Responses
ISG15 is a two-domain ubiquitin-like protein with at least two distinct biochemical functions in innate immunity. Intracellularly, IFN-α/β signaling induces the expression and conjugation of ISG15 to a wide variety of substrates proteins, a function important in anti-viral responses. ISG15 also has a surprising extracellular function, whereby free ISG15 synergizes with IL12 to stimulate the release of IFN-γ from Natural Killer (NK) cells. The extracellular function is poorly understood at the molecular level, but its importance was established through the identification and characterization of ISG15-deficient patents susceptible to Mycobacterial disease. Progress in characterizing both the canonical and non-canonical functions of ISG15 will be presented.
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