Ube2c, the ubiquitin-conjugating enzyme E2C, is essential for controlling cell cycle progression. It mediates ubiquitylation chain formation via the K11 linkage and is involved in multiple cellular pathways related to cell growth, apoptosis, and autophagy [1,2]. Genetic models, especially knockout (KO) and conditional knockout (CKO) mouse models, have been crucial in understanding its in-vivo functions.

In lung cancer cells with Kras mutations, Ube2c deletion significantly inhibited tumor formation and extended the lifespan of mice, revealing its role in tumorigenesis through the UBE2C/CDH1/DEPTOR axis which activates mTORC signaling [2]. In BMSCs and osteoblasts, conditional Ube2c deletion in mice led to reduced skeletal bone mass, impaired bone repair, decreased BMSC proliferation, enhanced osteoclastic activity, and reduced osteogenic differentiation, suggesting its importance in bone formation via stabilizing SMAD1/5 [3]. In acute myeloid leukemia (AML), knockdown of Ube2c in leukemia cell lines inhibited cell viability, promoted apoptosis, increased cellular Fe2+ and ROS levels, and enhanced erastin-induced ferroptosis, while also suppressing tumor formation in a mouse model, indicating its role in promoting AML cell proliferation through PI3K/AKT activation [4].

In conclusion, Ube2c plays essential roles in cell cycle regulation, tumorigenesis, and bone formation as revealed through KO and CKO mouse models. In the context of diseases, it significantly impacts lung cancer, AML, and bone-related conditions, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Domentean, Stefani, Paisana, Eunice, Cascão, Rita, Faria, Claudia C. 2023. Role of UBE2C in Brain Cancer Invasion and Dissemination. In International journal of molecular sciences, 24, . doi:10.3390/ijms242115792. https://pubmed.ncbi.nlm.nih.gov/37958776/

2. Zhang, Shizhen, You, Xiahong, Zheng, Yawen, Xiong, Xiufang, Sun, Yi. 2023. The UBE2C/CDH1/DEPTOR axis is an oncogene and tumor suppressor cascade in lung cancer cells. In The Journal of clinical investigation, 133, . doi:10.1172/JCI162434. https://pubmed.ncbi.nlm.nih.gov/36548081/

3. Zhang, Hui, Du, Yangge, Lu, Dazhuang, Zhou, Yongsheng, Zhang, Ping. 2024. UBE2C orchestrates bone formation through stabilization of SMAD1/5. In Bone, 187, 117175. doi:10.1016/j.bone.2024.117175. https://pubmed.ncbi.nlm.nih.gov/38917963/

4. Wang, Li, Zhao, Shuqin, Wang, Yongling, Liu, Jianying, Wang, Xiaoli. 2024. UBE2C promotes the proliferation of acute myeloid leukemia cells through PI3K/AKT activation. In BMC cancer, 24, 497. doi:10.1186/s12885-024-12212-x. https://pubmed.ncbi.nlm.nih.gov/38637730/