Selenoo-KO Mouse

SELENOO, also known as selenoprotein O and SELO, is an evolutionarily conserved selenoprotein. It catalyzes a posttranslational protein modification called AMPylation, which is essential for the oxidative stress response in bacteria and yeast. SELENOO localizes to the mitochondria and AMPylates proteins involved in redox homeostasis, thus playing a crucial role in the proper cellular response to oxidative stress [2].

In melanoma research, a murine model of spontaneous melanoma metastasis was used. SELENOO deficiency significantly reduced metastasis to distant visceral organs, an effect that could be rescued by treatment with the antioxidant N-acetylcysteine. Mechanistically, SELENOO AMPylated multiple mitochondrial substrates, including succinate dehydrogenase subunit A of mitochondrial complex II, and SELENOO-deficient cells had increased mitochondrial complex II activity. These findings suggest that SELENOO promotes cancer metastasis by modulating mitochondrial function and oxidative stress [1].

In conclusion, SELENOO is important for redox-related cellular responses through its AMPylation activity. The study of SELENOO-deficient mouse models has revealed its role in promoting melanoma metastasis, highlighting its significance in understanding cancer progression and the potential for targeting SELENOO-mediated posttranslational modification of mitochondrial substrates for cancer 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/