Title : FAM49B inhibits TRAF6 ubiquitination and alleviates liver ischemia reperfusion injury

Background: Hepatic ischemia-reperfusion occurs following liver transplantation and various liver surgeries. The ubiquitin chain inflammatory response mediated by TRAF6 is a crucial molecular step. How to target TRAF6 in order to inhibit the phosphorylation of the IKK inflammatory complex has been our long-term focus of research.

Method: We established a classic mouse liver IRI model and used a time point of 1/6 hour. Immunoprecipitation was used to identify direct interactions between proteins. The expression of proteins from diferent subcellular localizations was detected by Western blotting. Cell translocation was directly observed by immunofuorescence. HE, TUNEL and ELISA were performed for function tests.

Result: FAM49B was significantly downregulated in the liver IRI model. Overexpression of FAM49B could significantly reduce the phosphorylation of nuclear factor kappa-B kinase inhibitors (IKK) and downstream pro-inflammatory proteins. Mechanistically, FAM49B directly interacts with TRAF6, resulting in a decrease in the ubiquitination level of TRAF6. The use of IKK activators can significantly reverse the function of FAM49B.

Conclusion: We initially evaluated the function of FAM49B in liver ischemia-reperfusion injury (IRI) and demonstrated that its interaction with TRAF6 has a crucial impact on the IKK-mediated inflammatory cascade reaction.

Yanhong Yang is the head nurse of the Hepatobiliary and Pancreatic Tumor Center at Chongqing University Affiliated Cancer Hospital. She is in charge of the scientific research, teaching and clinical work of all the nurses in the department. She has extensive experience in clinical invasive procedures and patient care, particularly in the care of critically ill patients following liver, gallbladder and pancreatic surgeries.