Unc119b-KO Mouse

Unc119b is one of the paralogs of the guanine dissociation inhibitor-like solubilizing factors UNC119 in the human genome. It binds to N-myristoylated proteins, facilitating their trafficking between different membranes, and is involved in shuttling and sorting lipid-modified proteins to the primary cilium [2,3,4]. This process is crucial for maintaining the distinct composition of the cilium.

In hepatocellular carcinoma (HCC), a Cox model including Unc119b suggested unfavorable overall survival in the high-risk score group, and it was related to large tumor size, poor pathological grade, and advanced stage. Unc119b was also found to inhibit NK cell and TIL cell infiltration, impair Type-I and II IFN responses, and contribute to chemotherapy resistance in HCC, indicating it might be a novel therapeutic target for HCC [1]. In zebrafish, upregulation of unc119b was associated with genetic compensation for cilia defects in cep290 mutants, rescuing some cilia-related phenotypes [5].

In summary, Unc119b plays an essential role in the trafficking of myristoylated proteins, especially to the primary cilium. Its dysregulation is linked to diseases such as HCC, and studies in zebrafish have shown its potential in genetic compensation for cilia-related defects. Research on Unc119b provides insights into the molecular mechanisms of these biological processes and disease conditions, potentially leading to new therapeutic strategies for related diseases.

References:

1. Wu, Qinjuan, Li, Xin, Long, Menghong, Xie, Xianfeng, Liu, Qing. 2023. Integrated analysis of histone lysine lactylation (Kla)-specific genes suggests that NR6A1, OSBP2 and UNC119B are novel therapeutic targets for hepatocellular carcinoma. In Scientific reports, 13, 18642. doi:10.1038/s41598-023-46057-4. https://pubmed.ncbi.nlm.nih.gov/37903971/

2. Yelland, Tamas, Garcia, Esther, Samarakoon, Youhani, Ismail, Shehab. 2021. The Structural and Biochemical Characterization of UNC119B Cargo Binding and Release Mechanisms. In Biochemistry, 60, 1952-63. doi:10.1021/acs.biochem.1c00251. https://pubmed.ncbi.nlm.nih.gov/34130453/

3. Stephen, Louise A, Ismail, Shehab. . Shuttling and sorting lipid-modified cargo into the cilia. In Biochemical Society transactions, 44, 1273-1280. doi:. https://pubmed.ncbi.nlm.nih.gov/27911709/

4. Constantine, Ryan, Zhang, Houbin, Gerstner, Cecilia D, Frederick, Jeanne M, Baehr, Wolfgang. 2012. Uncoordinated (UNC)119: coordinating the trafficking of myristoylated proteins. In Vision research, 75, 26-32. doi:10.1016/j.visres.2012.08.012. https://pubmed.ncbi.nlm.nih.gov/23000199/

5. Cardenas-Rodriguez, Magdalena, Austin-Tse, Christina, Bergboer, Judith G M, Sayer, John A, Drummond, Iain A. 2021. Genetic compensation for cilia defects in cep290 mutants by upregulation of cilia-associated small GTPases. In Journal of cell science, 134, . doi:10.1242/jcs.258568. https://pubmed.ncbi.nlm.nih.gov/34155518/