Selenok, also known as selenoprotein K, is an endoplasmic reticulum (ER) transmembrane selenoprotein. It plays crucial roles in multiple biological processes, including ER stress regulation, calcium flux modulation, antioxidant defense, and protein palmitoylation. It is associated with pathways related to immune response, cell migration, phagocytosis, and is potentially linked to diseases like Alzheimer's disease (AD), cancer, and neurodegenerative disorders. Genetic models, such as knockout mouse models, have been instrumental in studying its functions [2,3,4,5].

In AD research, SELENOK-deficiency in 5xFAD mice inhibited microglial Aβ phagocytosis, exacerbating cognitive deficits, which were reversed by SELENOK overexpression. Mechanistically, SELENOK is involved in CD36 palmitoylation through DHHC6, regulating CD36 localization to microglial plasma membranes and thus impacting Aβ phagocytosis [1]. In cervical cancer cells, SELENOK knockdown enhanced ROS levels and iron-dependent lipid peroxidation, downregulated cell viability and proliferation, and shrank tumor size by inducing ferroptosis [2]. In skeletal muscle satellite cells (SMSCs) of chicken, SELENOK knockdown inhibited SMSCs proliferation and differentiation by activating ER stress signaling pathways triggered by intracellular Ca2+ dyshomeostasis, ultimately leading to apoptosis [3].

In conclusion, Selenok is essential for maintaining normal cellular functions. Its role in processes like microglial function in AD, ferroptosis in cervical cancer, and SMSCs development in chicken has been revealed through model-based research. The study of Selenok KO models has provided valuable insights into its functions and its potential as a therapeutic target in related disease areas.

References:

1. Ouyang, Pei, Cai, Zhiyu, Peng, Jiaying, Song, Guoli, Zhang, Zhonghao. 2024. SELENOK-dependent CD36 palmitoylation regulates microglial functions and Aβ phagocytosis. In Redox biology, 70, 103064. doi:10.1016/j.redox.2024.103064. https://pubmed.ncbi.nlm.nih.gov/38320455/

2. Abdurahman, Anwar, Li, Yu, Jia, Shi-Zheng, Xu, Ying, Song, Guo-Li. . Knockdown of the SELENOK gene induces ferroptosis in cervical cancer cells. In Metallomics : integrated biometal science, 15, . doi:10.1093/mtomcs/mfad019. https://pubmed.ncbi.nlm.nih.gov/36921994/

3. Fan, Rui-Feng, Chen, Xue-Wei, Cui, Han, Li, Jiu-Zhi, Lin, Hai. 2023. Selenoprotein K knockdown induces apoptosis in skeletal muscle satellite cells via calcium dyshomeostasis-mediated endoplasmic reticulum stress. In Poultry science, 102, 103053. doi:10.1016/j.psj.2023.103053. https://pubmed.ncbi.nlm.nih.gov/37716231/

4. Marciel, Michael P, Hoffmann, Peter R. 2019. Molecular Mechanisms by Which Selenoprotein K Regulates Immunity and Cancer. In Biological trace element research, 192, 60-68. doi:10.1007/s12011-019-01774-8. https://pubmed.ncbi.nlm.nih.gov/31187393/

5. Odunsi, Atinuke, Kapitonova, Mariia A, Woodward, George, Liu, Jun, Rozovsky, Sharon. 2024. Selenoprotein K at the intersection of cellular pathways. In Archives of biochemistry and biophysics, 764, 110221. doi:10.1016/j.abb.2024.110221. https://pubmed.ncbi.nlm.nih.gov/39571956/