Regulation of p53 activity by methionine sulfoxide reductases

Regulation Of p53 Activity By Methionine Sulfoxide Reductases Aim: p53 is the most crucial tumor suppressor protein in humans, and it is involved in many biological functions such as cell cycle arrest, DNA repair, and apoptosis. Many post-translational mechanisms controlling p53 activity are known, but its control by oxidative stress is not clearly known. The methionine amino acids in the structure of p53 form methionine sulfoxide groups (metO) in an oxidation state, which disrupts the function of p53. Methionine Sulfoxide Reductases, which are antioxidant group enzymes, reduce methionine sulfoxides back to methionine. The purpose of this project is to determine whether there is an activity control mechanism in which Msr group enzymes play a role by methionine oxidation / reduction on p53. Material and Method: The effect of Msr enzymes on p53 activity has been studied in yeast cells under normal conditions and oxidative stress conditions. Results: Mutants that lack methionine sulfoxide reductase genes had slightly higher p53 dependent LacZ activity than control cells. However, overexpression of MSR genes did not change p53 activity. The mutants had a different p53 activity pattern under oxidative stress when the cells treated with 1 mM of hydrogen peroxide. Specifically, the cells that lack both MSRA and MSRB genes showed less p53 activity. Conslusion: The loss of activity occurring in p53 in the oxidative stress has resulted from the protection and control of Msr enzymes. Keywords: Methionine Sulfoxide Reductase, Transcription, p53, Oxidative Stress, Antioxidant, Regulation