Gene Number: 7157

Location: 17p13.1

Key Functions: Tumor suppression, DNA damage response, cell cycle regulation, apoptosis induction, genomic stability maintenance

TP53 encodes tumor protein p53, a transcription factor that serves as a central guardian of cellular integrity. Often referred to as the “guardian of the genome,” p53 is activated in response to various cellular stressors, including DNA damage, oncogene activation, hypoxia, and oxidative stress. Upon activation, p53 binds specific DNA sequences to regulate the transcription of a wide array of target genes that govern cell cycle arrest, DNA repair, apoptosis, and senescence—mechanisms essential for maintaining genomic stability and preventing malignant transformation [R].

Through its transcriptional activity, p53 halts the cell cycle primarily at the G1/S checkpoint by upregulating CDKN1A (p21), allowing time for DNA repair before replication proceeds. When damage is irreparable, p53 induces apoptosis via activation of pro-apoptotic genes such as BAX, PUMA, and NOXA, thereby eliminating potentially oncogenic cells. p53 also exerts non-transcriptional roles within mitochondria, directly influencing apoptotic signaling and metabolic regulation [R].

Beyond its classical role in tumor suppression, p53 is involved in cellular metabolism, autophagy, ferroptosis, and modulation of the immune response, underscoring its multifaceted contribution to organismal homeostasis. Its regulatory network is tightly controlled by MDM2, an E3 ubiquitin ligase that mediates p53 degradation under normal conditions, thus preventing unwarranted cell cycle arrest or apoptosis [R].

Loss, mutation, or dysregulation of TP53 is one of the most frequent events in human malignancies, observed in over half of all cancers. Mutant forms of p53 often lose their tumor-suppressive functions and may acquire oncogenic gain-of-function properties, promoting tumor progression, metastasis, and therapeutic resistance. The clinical impact of TP53 dysfunction extends across nearly all cancer types, making it a cornerstone of cancer biology and a critical target for therapeutic development [R].