Ube2o, the ubiquitin-conjugating enzyme E2 O, is an atypical ubiquitin-conjugating enzyme with E2-E3 hybrid enzyme activity. It is involved in multiple biological processes such as controlling the quality of the cell proteome, including protein degradation, modification, transport, and location. It participates in regulating signaling pathways like BMP/SMAD, TRAF/NF-κB, mTOR/HIF1a, and IL-1β/IRAK4, thus being of great biological importance [2].

In hepatocellular carcinoma (HCC), Ube2o deficiency inhibits HCC growth and metastasis both in vitro and in vivo. Liver-specific deletion of Ube2o in mice makes them resistant to DEN-induced hepatocarcinogenesis, along with up-regulation of HADHA and reduced hepatic lipid accumulation, indicating Ube2o promotes lipid metabolic reprogramming and HCC progression by mediating HADHA ubiquitination [1]. In osteosarcoma, multi-monoubiquitination of L3MBTL2 by Ube2O results in its proteasomal degradation, and the UBE2O/L3MBTL2 axis is crucial for osteosarcoma growth. Pharmacological blockage of Ube2O by arsenic trioxide can enhance L3MBTL2-induced condensates and suppress osteosarcoma growth [3].

In conclusion, Ube2o is an important regulator in various biological processes and diseases. The gene knockout or conditional knockout mouse models have revealed its role in promoting the development of cancers such as HCC and osteosarcoma, highlighting its potential as a therapeutic target in these disease areas.