The article discusses the complex regulation of p53, a tumor suppressor protein, and its response to various internal and external signals. p53 integrates signals from the cell's environment to protect against neoplastic transformation. The regulation of p53 primarily occurs at the protein level, with modifications affecting its stability, function, and interaction with other proteins. Key mechanisms include phosphorylation, acetylation, and redox modulation. Post-translational modifications can affect p53's DNA binding, transcriptional activity, and oligomerization. The article also highlights the importance of binding proteins that modulate p53 activity, such as Mdm2, HIF-1α, and Ref-1. Different stimuli, like ionizing radiation (IR), ultraviolet radiation (UV), hypoxia, and cell adhesion, induce p53 through distinct signaling pathways, each involving specific post-translational modifications. Understanding these pathways is crucial for developing targeted modulators of p53 activity to prevent tissue damage or restore sensitivity to anti-cancer therapies.The article discusses the complex regulation of p53, a tumor suppressor protein, and its response to various internal and external signals. p53 integrates signals from the cell's environment to protect against neoplastic transformation. The regulation of p53 primarily occurs at the protein level, with modifications affecting its stability, function, and interaction with other proteins. Key mechanisms include phosphorylation, acetylation, and redox modulation. Post-translational modifications can affect p53's DNA binding, transcriptional activity, and oligomerization. The article also highlights the importance of binding proteins that modulate p53 activity, such as Mdm2, HIF-1α, and Ref-1. Different stimuli, like ionizing radiation (IR), ultraviolet radiation (UV), hypoxia, and cell adhesion, induce p53 through distinct signaling pathways, each involving specific post-translational modifications. Understanding these pathways is crucial for developing targeted modulators of p53 activity to prevent tissue damage or restore sensitivity to anti-cancer therapies.