Contribution of p53, p63, and p73 to the developmental diseases and cancer

Area of Science:

• Molecular biology
• Genetics
• Oncology

Background:

• The TP53 gene, a critical tumor suppressor, is frequently mutated in human cancers, leading to Li-Fraumeni syndrome when inactivated by germline mutations.
• TP53 inactivation is implicated in a wide range of malignancies, with p53 protein's tumor suppressive role confirmed in animal models.
• The homologous genes TP63 and TP73, discovered later, are involved in development, but their roles in tumorigenesis remain debated.

Purpose of the Study:

• To review the contribution of p53, p63, and p73 proteins to human pathology.
• To emphasize the distinct roles of these proteins in both normal development and cancer formation.
• To explore the controversial functions of p63 and p73 in tumorigenesis.

Main Methods:

• Literature review of studies on TP53, TP63, and TP73.
• Analysis of animal models with genetic alterations in these genes.
• Examination of human genetic data linking mutations to diseases.

Main Results:

• p53 is essential for tumor suppression, with its deficiency leading to early-onset cancers.
• p73 is important for neurogenesis and homeostasis, while p63 is critical for stratified epithelial development.
• While p63 and p73 knockout animals are not consistently tumor-prone, their roles in cancer are complex and debated.
• Germline mutations in TP63 are associated with human developmental disorders, unlike the rarity of mutations in TP63 and TP73.

Conclusions:

• p53, p63, and p73 have distinct and vital roles in human development and disease.
• Understanding the differential functions of these genes is crucial for comprehending tumorigenesis and developing therapeutic strategies.
• Further research is needed to fully elucidate the complex interplay between these tumor suppressor genes in cancer development.