Abstract
The p53 tumor suppressor is a multi-domain protein. The proline-rich domain (PRD) resides next to the transactivation domains at the N-terminus and before the DNA binding domain. The PRD has been studied extensively for nearly three decades and has been shown to be a key component for the tumor suppressor functions of p53. However, study findings have not been analyzed systematically. Herein, we undertake a comprehensive review of the studies which examined the roles of the PRD in the biological functions, stability, and protein-protein interactions of p53. While p53 is one of the most frequently mutated cellular proteins in human cancer, mutation in its PRD is uncommon, which will be discussed. The importance of the PRD in regulation of mutant p53 has also been investigated and will be reviewed as well. In addition, one of the amino acids in the PRD in human p53 is polymorphic. Information about the polymorphism and its impact on p53 function and association with disease outcomes will also be reviewed. Collectively, studies to date demonstrate that the PRD is a multifunctional domain critical for a variety of p53 functions as well as p53 stability, and that the PRD polymorphism is a potential biomarker of cancer risk and cancer outcome. Its involvement in regulation of both wild-type and mutant p53 offers opportunities for potential development of novel cancer therapeutic strategies.