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Research study by Dr. Jian Zhang and colleagues on the control of sepsis is published in the Journal of Experimental Medicine

February 5, 2020

Dr. Jian Zhang

Sepsis, a systemic inflammatory response syndrome (SIRS) in patients following infection or injury, causes millions of deaths globally each year. The release of IL-1β and the induction of pyroptosis during sepsis is tightly controlled by a multi-protein complex, termed the NLRP3 inflammasome. Hyper-activation of NLRP3 inflammasomes contributes to the development of endotoxemia and sepsis, but the molecular mechanisms are poorly defined. Dr. Zhang’s laboratory together with colleagues at the Ohio State University identified RNF125 and Cbl-b as the key E3 ubiquitin ligases that keep the NLRP3 inflammasomes in check by targeting NLRP3 for sequential K63- and K48-linked polyubiquitination of NLRP3. This event is essential for keeping the NLRP3 inflammasomes under control and ultimately restraining endotoxemia and polymicrobial sepsis. The molecular insights gained in this study will provide novel targets for modulating NLRP3 inflammasome-mediated sepsis in patients. This study was published online in the Journal of Experimental Medicine.

The full title of the study is: Sequential ubiquitination of NLRP3 by RNF125 and Cbl-b limits inflammasome activation and endotoxemia