Zdhhc12, a zinc finger DHHC-type palmitoyltransferase, plays a crucial role in protein S-palmitoylation, a post-translational modification. This modification is involved in diverse biological processes such as regulating protein stability, localization, and function within cells. It is associated with pathways related to inflammation, tumorigenesis, and innate immune responses [1-10]. Genetic models, like gene knockout (KO) mouse models, are valuable tools to study Zdhhc12's functions.

In KO mouse models, Zdhhc12 deficiency enhances inflammatory symptoms and lethality following alum-induced peritonitis and LPS-induced endotoxic shock, indicating its role in suppressing NLRP3 inflammasome-mediated inflammation [2]. In ovarian cancer, knockdown of Zdhhc12 inhibits claudin-3 (CLDN3) accurate membrane localization, protein stability, and ovarian cancer cell tumorigenesis, suggesting it promotes ovarian cancer progression through CLDN3 S-palmitoylation [1]. Also, in glioma cells, knockdown of Zdhhc12 reduces cell growth, migration, and invasion, showing its contribution to glioma malignancy [3].

In conclusion, Zdhhc12 is essential for regulating protein function through S-palmitoylation, influencing processes like inflammation and tumorigenesis. Studies using KO/CKO mouse models have revealed its role in inflammatory diseases such as sepsis-related inflammation and in cancer types like ovarian cancer and glioma, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Yuan, Meng, Chen, Xiaobing, Sun, Yitang, Cao, Ji, He, Qiaojun. 2020. ZDHHC12-mediated claudin-3 S-palmitoylation determines ovarian cancer progression. In Acta pharmaceutica Sinica. B, 10, 1426-1439. doi:10.1016/j.apsb.2020.03.008. https://pubmed.ncbi.nlm.nih.gov/32963941/

2. Wang, Liqiu, Cai, Jing, Zhao, Xin, Jin, Shouheng, Cui, Jun. 2022. Palmitoylation prevents sustained inflammation by limiting NLRP3 inflammasome activation through chaperone-mediated autophagy. In Molecular cell, 83, 281-297.e10. doi:10.1016/j.molcel.2022.12.002. https://pubmed.ncbi.nlm.nih.gov/36586411/

3. Lu, Feng, Shen, Shang-Hang, Wu, Shizhong, Zeng, Guangming, Wei, De. . Hypomethylation-induced prognostic marker zinc finger DHHC-type palmitoyltransferase 12 contributes to glioblastoma progression. In Annals of translational medicine, 10, 334. doi:10.21037/atm-22-520. https://pubmed.ncbi.nlm.nih.gov/35434031/