Ube2g1-KO Mouse

Ube2g1, the ubiquitin-conjugating enzyme E2G1, is a key factor in the ubiquitination process, which is closely related to the post-translation modification of proteins. Ubiquitination plays vital roles in many cellular processes such as immune defense, cell cycle regulation, and protein degradation pathways [2,3,4,5,6].

In the context of osteoarthritis (OA), circRNA-UBE2G1, which is associated with the Ube2g1 gene, was found to be upregulated in OA tissues. Function assays indicated that its inhibition could reduce the effects of LPS on C28/I2 cells viability and apoptosis, and it was shown to act via the miR-373/HIF-1a axis [1]. In large yellow croaker, the LcUbe2g1 was significantly activated by the infection of Pseudomonas plecoglossicida, and it interacted with NEDD8 to co-regulate the ubiquitination process, playing a crucial role in the immune response against this infection [2]. In multiple myeloma, UBE2G1 cooperated with UBE2D3 to promote the K48-linked polyubiquitination of CRL4CRBN neomorphic substrates. Blockade of UBE2G1 diminished the ubiquitination and degradation of these substrates and the consequent antitumor activities of tested cereblon-modulating agents, highlighting its importance in drug-induced protein degradation and potential drug resistance [3,6].

In summary, Ube2g1 is essential in ubiquitination-related biological functions. Its role in diseases such as osteoarthritis, infectious diseases in fish, and multiple myeloma has been revealed through various functional studies. Understanding Ube2g1's functions contributes to a better understanding of disease mechanisms and may provide potential therapeutic targets for these diseases.

References:

1. Chen, Guang, Liu, Tao, Yu, Bofan, Wang, Bingyi, Peng, Qiang. 2020. CircRNA-UBE2G1 regulates LPS-induced osteoarthritis through miR-373/HIF-1a axis. In Cell cycle (Georgetown, Tex.), 19, 1696-1705. doi:10.1080/15384101.2020.1772545. https://pubmed.ncbi.nlm.nih.gov/32476580/

2. Peng, Jia, Li, Wanbo, Wang, Bi, Han, Fang, Wang, Zhiyong. 2022. UBE2G1 Is a Critical Component of Immune Response to the Infection of Pseudomonas Plecoglossicida in Large Yellow Croaker (Larimichthys crocea). In International journal of molecular sciences, 23, . doi:10.3390/ijms23158298. https://pubmed.ncbi.nlm.nih.gov/35955424/

3. Lu, Gang, Weng, Stephanie, Matyskiela, Mary, Chamberlain, Philip, Rolfe, Mark. 2018. UBE2G1 governs the destruction of cereblon neomorphic substrates. In eLife, 7, . doi:10.7554/eLife.40958. https://pubmed.ncbi.nlm.nih.gov/30234487/

4. Masuda, Shusaku, Kurabayashi, Nobuhiro, Nunokawa, Rina, Yoshitane, Hikari, Fukada, Yoshitaka. 2024. TRAF7 determines circadian period through ubiquitination and degradation of DBP. In Communications biology, 7, 1280. doi:10.1038/s42003-024-07002-x. https://pubmed.ncbi.nlm.nih.gov/39379486/

5. Choi, Yun-Seok, Lee, Yun-Ju, Lee, Seo-Yeon, Cohen, Robert E, Ryu, Kyoung-Seok. 2014. Differential ubiquitin binding by the acidic loops of Ube2g1 and Ube2r1 enzymes distinguishes their Lys-48-ubiquitylation activities. In The Journal of biological chemistry, 290, 2251-63. doi:10.1074/jbc.M114.624809. https://pubmed.ncbi.nlm.nih.gov/25471371/

6. Sievers, Quinlan L, Gasser, Jessica A, Cowley, Glenn S, Fischer, Eric S, Ebert, Benjamin L. 2018. Genome-wide screen identifies cullin-RING ligase machinery required for lenalidomide-dependent CRL4CRBN activity. In Blood, 132, 1293-1303. doi:10.1182/blood-2018-01-821769. https://pubmed.ncbi.nlm.nih.gov/30042095/