Zdhhc11-KO Mouse

ZDHHC11, a member of the DHHC palmitoyl transferase family, plays a crucial role in various biological processes. It is involved in protein palmitoylation, a significant post-translational modification. This modification is implicated in multiple biological pathways, including those related to immune responses and cell growth regulation. Genetic models, such as KO mouse models, have been valuable in studying ZDHHC11's functions [1-4, 6-9].

In terms of specific findings, Zdhhc11 knockout mice showed a lower level of serum IL6 upon treatment with LPS and D-galactosamine or HSV-1 infection, indicating that ZDHHC11 positively regulates NF-κB signaling by enhancing TRAF6 oligomerization [1]. Zdhhc11-/-mice also exhibited lower serum cytokine levels and higher lethality after HSV-1 infection, suggesting its importance in mediating MITA-dependent innate immune responses against DNA viruses [3]. In hepatocyte cultures and mice, zDHHC11 regulates lipid droplet catabolism by modifying adipose triacylglyceride lipase (ATGL) [4]. In Burkitt lymphoma (BL), knockdown of circZDHHC11, a transcript of ZDHHC11 gene, strongly inhibited BL growth [2]. In Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL), knockdown of ZDHHC11 decreased cell growth [5]. In colorectal cancer, knockdown of ZDHHC11 suppressed cell growth [6].

In conclusion, ZDHHC11 is essential for regulating immune responses, lipid droplet homeostasis, and cell growth in various diseases. The use of Zdhhc11 KO mouse models has been instrumental in revealing its role in diseases such as viral infections, lymphoma, and colorectal cancer, providing insights into potential therapeutic targets.

References:

1. Liu, Enping, Sun, Jiawei, Yang, Jing, Chen, Dahua, Sun, Qinmiao. 2021. ZDHHC11 Positively Regulates NF-κB Activation by Enhancing TRAF6 Oligomerization. In Frontiers in cell and developmental biology, 9, 710967. doi:10.3389/fcell.2021.710967. https://pubmed.ncbi.nlm.nih.gov/34490261/

2. Liu, Yichen, Zhao, Xing, Seitz, Annika, Ziel-Swier, Lotteke J Y M, Kluiver, Joost. 2024. Circular ZDHHC11 supports Burkitt lymphoma growth independent of its miR-150 binding capacity. In Scientific reports, 14, 8730. doi:10.1038/s41598-024-59443-3. https://pubmed.ncbi.nlm.nih.gov/38627588/

3. Liu, Ying, Zhou, Qian, Zhong, Li, Shu, Hong-Bing, Li, Shu. 2018. ZDHHC11 modulates innate immune response to DNA virus by mediating MITA-IRF3 association. In Cellular & molecular immunology, 15, 907-916. doi:10.1038/cmi.2017.146. https://pubmed.ncbi.nlm.nih.gov/29429998/

4. Zheng, Yuping, Chen, Jishun, Macwan, Vinitha, Fairn, Gregory D, Neculai, Dante. 2024. S-acylation of ATGL is required for lipid droplet homoeostasis in hepatocytes. In Nature metabolism, 6, 1549-1565. doi:10.1038/s42255-024-01085-w. https://pubmed.ncbi.nlm.nih.gov/39143266/

5. Ziel-Swier, Lotteke J Y M, Liu, Yichen, Seitz, Annika, van den Berg, Anke, Kluiver, Joost. 2022. The Role of the MYC/miR-150/MYB/ZDHHC11 Network in Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma. In Genes, 13, . doi:10.3390/genes13020227. https://pubmed.ncbi.nlm.nih.gov/35205272/

6. Murakami, Yuki, Konishi, Hiroaki, Fujiya, Mikihiro, Tanabe, Hiroki, Okumura, Toshikatsu. 2022. Testis-specific hnRNP is expressed in colorectal cancer cells and accelerates cell growth mediating ZDHHC11 mRNA stabilization. In Cancer medicine, 11, 3643-3656. doi:10.1002/cam4.4738. https://pubmed.ncbi.nlm.nih.gov/35384384/