Describe the ways in which the p53 tumor-suppressor protein can be activated in normal cells.

The p53 tumor-suppressor protein plays a crucial role in preventing cancer by regulating the cell cycle and acting as a tumor suppressor. In normal cells, p53 can be activated through various mechanisms, including DNA damage, cellular stress, and oncogene activation. Activation of p53 in response to DNA damage involves ATM and ATR kinases, which phosphorylate p53, resulting in cell cycle arrest, DNA repair, and apoptosis. Cellular stress, such as hypoxia, nutrient deprivation, and energy deprivation, can also activate p53 via the AMPK pathway. Additionally, oncogene activation can lead to replication stress and production of reactive oxygen species (ROS), activating the p53 protein. These mechanisms allow p53 to maintain genomic stability and protect cells from becoming cancerous.