TRIM47, a member of the tripartite motif-containing protein family, functions as an E3 ubiquitin ligase. It is involved in multiple biological pathways, such as the NF-κB, MAPK, and ubiquitin-proteasome systems, and plays a significant role in various physiological and pathological processes [1,2,3,4,5,6,7,8,9,10]. Genetic models, especially gene knockout (KO) and conditional knockout (CKO) mouse models, have been crucial for understanding its functions.

In lipopolysaccharide (LPS)-induced acute lung injury, TRIM47-deficient mice showed resistance to the injury and death by attenuating pulmonary inflammation. TRIM47 promoted endothelial activation through K63-linked ubiquitination of TRAF2, which activated the NF-κB and MAPK signaling pathways [1]. In hepatocellular carcinoma, knockdown of TRIM47 induced ferroptosis, mainly through the involvement of CDO1 to regulate GSH synthesis [2]. In gastric cancer, TRIM47 knockdown inhibited cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, it interacted with CYLD protein, promoting its K48-linked ubiquitination and degradation, thus activating the NF-κB pathway [6]. In prostate cancer, TRIM47 knockdown inhibited cell proliferation, cell cycle progression, migration, and invasion, while promoting apoptosis. It was shown to bind to MDM2 and regulate MDM2/p53 expression [9].

In conclusion, TRIM47 has diverse functions in different biological processes and disease conditions. KO/CKO mouse models have been instrumental in revealing its roles in diseases like acute lung injury, hepatocellular carcinoma, gastric cancer, and prostate cancer. These studies suggest that TRIM47 could potentially be a therapeutic target for these diseases.