Zdhhc1, also known as ZNF377, belongs to the palmitoyl-transferase ZDHHC family. Protein S-palmitoylation, a process Zdhhc1 is involved in, plays a critical role in many cellular processes such as protein-lipid interaction. It is associated with multiple biological pathways including those related to metabolism, cell death, and stem cell maintenance [1,2,3]. Genetic models, like knockout (KO) mouse models, are valuable for studying Zdhhc1's function.

In cancer research, restoration of Zdhhc1 expression curbs cancer cell progression. In colorectal cancer, its down-regulation is associated with unfavorable prognosis, and it inhibits cell proliferation and invasion in vitro and in vivo by downregulating LIPG via IGF2BP1 palmitoylation [2]. In localized prostate cancer, Zdhhc1 is identified as a pyroptosis inducer, and its promoting effect on pyroptosis was verified [5]. In atherosclerosis, Zdhhc1 deficiency in mice reduces foam cell formation and atherosclerotic plaque development by inhibiting the PI3K-Akt-mTOR signaling pathway [4]. In mammary gland development, Zdhhc1-mediated Gpm6a palmitoylation is essential for maintaining mammary stem cell activity [3]. Also, in THP-1 cells and mice, Zdhhc1 knockout inhibits foam cell formation [4].

In conclusion, Zdhhc1 is crucial for various biological functions including cell metabolism, cancer cell regulation, stem cell maintenance, and the development of atherosclerosis. The study of Zdhhc1 using KO/CKO mouse models has provided significant insights into its role in cancer, atherosclerosis, and mammary gland development, offering potential targets for therapeutic intervention in related diseases.

References:

1. Le, Xin, Mu, Junhao, Peng, Weiyan, Tao, Qian, Xiang, Tingxiu. 2020. DNA methylation downregulated ZDHHC1 suppresses tumor growth by altering cellular metabolism and inducing oxidative/ER stress-mediated apoptosis and pyroptosis. In Theranostics, 10, 9495-9511. doi:10.7150/thno.45631. https://pubmed.ncbi.nlm.nih.gov/32863941/

2. Zhang, Qun, Du, Zhouyuan, Zhou, Wei, Yu, Haixin, Liu, Tao. 2024. ZDHHC1 downregulates LIPG and inhibits colorectal cancer growth via IGF2BP1 Palmitoylation. In Cancer gene therapy, 31, 1427-1437. doi:10.1038/s41417-024-00808-1. https://pubmed.ncbi.nlm.nih.gov/39069526/

3. Chen, Weizhen, Guo, Luyao, Wei, Wei, Cai, Cheguo, Wu, Gaosong. 2024. Zdhhc1- and Zdhhc2-mediated Gpm6a palmitoylation is essential for maintenance of mammary stem cell activity. In Cell reports, 43, 114762. doi:10.1016/j.celrep.2024.114762. https://pubmed.ncbi.nlm.nih.gov/39321020/

4. Zhou, Binhui, Liu, Yang, Ma, Haoyuan, Li, Tianhan, Liang, Yinming. 2024. Zdhhc1 deficiency mitigates foam cell formation and atherosclerosis by inhibiting PI3K-Akt-mTOR signaling pathway through facilitating the nuclear translocation of p110α. In Biochimica et biophysica acta. Molecular basis of disease, 1871, 167577. doi:10.1016/j.bbadis.2024.167577. https://pubmed.ncbi.nlm.nih.gov/39566590/

5. Luo, Cheng-Gong, Gui, Cheng-Peng, Huang, Gao-Wei, Lu, Jun, Chen, Wei. 2022. Identification of ZDHHC1 as a Pyroptosis Inducer and Potential Target in the Establishment of Pyroptosis-Related Signature in Localized Prostate Cancer. In Oxidative medicine and cellular longevity, 2022, 5925817. doi:10.1155/2022/5925817. https://pubmed.ncbi.nlm.nih.gov/36589680/