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Inhibition of regulatory proteins allows for continuous cyclin/CDK activity and cell cycle progression in GBM cells. In healthy cells, FOXO and p53 can activate p27 and p21, respectively, and consequently induce cell cycle arrest to maintain homeostasis. DNA damage as a result of ROS accumulation is a key trigger for p21 activation. However, overactive Akt inhibits FOXO and p53, and therefore facilitates uncontrolled tumor cell growth and division.
