SELENOO, also known as selenoprotein O or SELO, is one of the 25 human selenoproteins incorporating selenocysteine. It functions as an evolutionarily conserved pseudokinase that catalyzes AMPylation, a post-translational protein modification, which is essential for the oxidative stress response [2,3]. SELENOO localizes to the mitochondria and may be involved in redox homeostasis pathways [2]. Understanding its function can be crucial for elucidating the role of selenoproteins in maintaining cellular health.

In melanoma, high SELENOO expression was correlated with metastasis and poor overall survival. In a murine model of spontaneous melanoma metastasis, SELENOO-deficient mice showed significantly reduced metastasis to distant visceral organs, and this could be rescued by the antioxidant N-acetylcysteine. Mechanistically, SELENOO AMPylated multiple mitochondrial substrates like succinate dehydrogenase subunit A, and SELENOO-deficient cells had increased mitochondrial complex II activity, indicating that SELENOO deficiency limits melanoma metastasis by modulating mitochondrial function and oxidative stress [1].

In conclusion, SELENOO is important for modulating mitochondrial function and oxidative stress, as revealed by the murine model of melanoma metastasis. The study of SELENOO knockout mouse models in melanoma provides insights into the role of this gene in cancer progression, highlighting its potential as a therapeutic target in melanoma treatment [1].

References:

1. Nascentes Melo, Luiza Martins, Sabatier, Marie, Ramesh, Vijayashree, Sreelatha, Anju, Tasdogan, Alpaslan. . Selenoprotein O Promotes Melanoma Metastasis and Regulates Mitochondrial Complex II Activity. In Cancer research, 85, 942-955. doi:10.1158/0008-5472.CAN-23-2194. https://pubmed.ncbi.nlm.nih.gov/39700395/

2. Sreelatha, Anju, Yee, Samantha S, Lopez, Victor A, Tomchick, Diana R, Tagliabracci, Vincent S. 2018. Protein AMPylation by an Evolutionarily Conserved Pseudokinase. In Cell, 175, 809-821.e19. doi:10.1016/j.cell.2018.08.046. https://pubmed.ncbi.nlm.nih.gov/30270044/

3. Mukherjee, Meghomukta, Sreelatha, Anju. 2021. Identification of selenoprotein O substrates using a biotinylated ATP analog. In Methods in enzymology, 662, 275-296. doi:10.1016/bs.mie.2021.10.001. https://pubmed.ncbi.nlm.nih.gov/35101215/