Trim8-flox Mouse

Trim8, a member of the TRIM family proteins, is an E3 ubiquitin ligase. It is involved in multiple cellular processes such as cell survival, carcinogenesis, autophagy, apoptosis, differentiation, and inflammation [3,4]. Trim8 exerts its functions through regulating pivotal cellular signaling pathways including the p53 tumor suppressor, NF-κB, and JAK-STAT pathways [4,5].

In non-alcoholic fatty liver disease (NAFLD), TRIM8 forms an E3 ligase complex with TRIB3, which catalyzes K48-linked polyubiquitination of hepatic nuclear factor 4α (HNF4α) on lysine 470, leading to HNF4α degradation and NAFLD progression. Abrogating this degradation attenuated the effect of TRIB3 in a diet-induced NAFLD model [1]. In Ewing sarcoma, TRIM8 ubiquitinates and degrades EWS/FLI, a driver fusion-TF. TRIM8 knockout led to increased EWS/FLI protein levels, which was not tolerated by the cells [2]. In adipocyte inflammation and insulin resistance, inhibiting TRIM8 alleviates the conditions by regulating the DUSP14/MAPKs pathway [6].

In conclusion, Trim8 plays crucial roles in various biological processes and diseases. Through gene knockout studies in models like mice, its functions in disease-related pathways such as in NAFLD, Ewing sarcoma, and adipocyte-related metabolic disorders have been revealed. These findings contribute to understanding disease mechanisms and developing potential therapeutic strategies.