p53proteiinin

The p53 protein, often referred to as the "guardian of the genome," is a crucial tumor suppressor protein that plays a central role in regulating the cell cycle, DNA repair, and programmed cell death (apoptosis). It is encoded by the *TP53* gene, located on the short arm of chromosome 17 (17p13.1). As a transcription factor, p53 activates or represses the expression of numerous genes involved in cellular responses to stress, such as DNA damage, hypoxia, and oncogenic signaling.

Under normal conditions, p53 levels are kept low due to rapid degradation mediated by the E3 ubiquitin ligase MDM2, which targets p53 for proteasomal breakdown. However, when cells experience DNA damage or other forms of stress, post-translational modifications—such as phosphorylation, acetylation, and ubiquitination—stabilize p53, allowing it to accumulate and exert its functions. Once activated, p53 induces cell cycle arrest at the G1/S checkpoint, enabling DNA repair mechanisms to correct errors. If the damage is irreparable, p53 promotes apoptosis to prevent the propagation of genetically compromised cells.

Mutations in the *TP53* gene are among the most common alterations in human cancers, often leading to loss-of-function mutations that disable p53’s tumor-suppressive activity. These mutations can result in uncontrolled cell proliferation, genomic instability, and resistance to chemotherapy. Gain-of-function mutations, where p53 acquires oncogenic properties, have also been observed in certain cancers, further contributing to tumorigenesis.

Beyond its role in cancer, p53 is involved in aging, metabolic regulation, and responses to oxidative stress. Its importance is underscored by the fact that p53 knockout mice develop tumors rapidly, demonstrating its essential role in maintaining genomic integrity. Research into p53 continues to explore its potential as a therapeutic target, including strategies to reactivate wild-type p53 or inhibit mutant p53 in cancer treatment.