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Published on: February 28, 2025
USP18-mediated protein deISGylation and its role in tuberculosis and other infectious diseases
Qi-Ao Zhang1, Zi-Lu Wang1, Pei-Bo Li2
1Institute of Modern Biopharmaceuticals,State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Chongqing 400715, China.
Abstract:
The transcription of interferon-stimulated gene 15 (isg15) is induced by type I interferons. ISG15 can covalently modify target proteins through the sequential action of enzymesE1, E2, and E3, a process known as ISGylation. The ISGylation of host proteins is widely involved in immune responses, such as host antiviral defence. Ubiquitin-specific protease 18 (USP18), as a deubiquitinase (DUB), can remove ISG15 conjugated to target proteins and inhibit host immune responses by suppressing the type I interferon signaling. The dynamic balance between ISGylation and deISGylation mediated by ISG15 or USP18 respectively plays a significant role in the tuberculosis. Furthermore, similar to ISG15, USP18 is extensively involved in virus-host interaction. In this review, we summarize the roles of ISGylation and deISGylation in tuberculosis and other important diseases mediated by ISG15 and USP18 respectively, underlying regulator network. Further studies in this aspect will inspire new host-targeted strategies to control important diseases such as tuberculosis.
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