Zdhhc24, a palmitoyl-transferase, plays a crucial role in palmitoylation processes. Palmitoylation is an important post-translational modification that can affect protein localization, stability, and function. Zdhhc24 is associated with pathways such as the PI3K-AKT pathway and the antiviral innate immune response pathway, which are vital for metabolic homeostasis and defense against viral infections respectively [1,2]. Genetic models, like knockout mice, are valuable tools for studying Zdhhc24's function.

In the context of high-fat diet-induced liver tumorigenesis, Zdhhc24 knockout mice were used. The results showed that Zdhhc24, along with Zdhhc17, palmitoylates AKT. This palmitoylation anchors AKT to the cell membrane, activating it and promoting non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). A high-fat diet was found to enhance this process [1]. In antiviral innate immunity, Zdhhc24 catalyzes the palmitoylation of mitochondrial antiviral signaling protein (MAVS). This promotes the activation of the TBK1-IRF3-interferon (IFN) pathway, leading to antiviral immune responses, especially under conditions of palmitic acid (PA) stimulation or in high-fat-diet-fed mouse models [2].

In conclusion, Zdhhc24 is essential for palmitoylation-mediated activation of proteins in key biological pathways. The use of Zdhhc24 knockout mouse models has revealed its significant role in liver tumorigenesis and antiviral innate immunity, providing insights into potential therapeutic strategies for related diseases such as HCC and viral infections [1,2].

References:

1. Bu, Lang, Zhang, Zhengkun, Chen, Jianwen, Kuang, Ming, Guo, Jianping. 2024. High-fat diet promotes liver tumorigenesis via palmitoylation and activation of AKT. In Gut, 73, 1156-1168. doi:10.1136/gutjnl-2023-330826. https://pubmed.ncbi.nlm.nih.gov/38191266/

2. Bu, Lang, Wang, Huan, Zhang, Shuishen, Cheng, Chao, Guo, Jianping. 2024. Targeting APT2 improves MAVS palmitoylation and antiviral innate immunity. In Molecular cell, 84, 3513-3529.e5. doi:10.1016/j.molcel.2024.08.014. https://pubmed.ncbi.nlm.nih.gov/39255795/