Repair or perish – the role of p53 protein in a cell’s life

Abstract

The p53 protein is one of the most important suppressors of neoplastic transformation. It regulates transcription of mul­tiple genes and interacts directly with other proteins. It plays a significant role in the most important processes that take place in the cell, including: DNA repair, cell cycle and programmed cell death – apoptosis. Loss of its proper function leads to a disturbance of the mechanisms controlling cell proliferation and survival, which contributes to the development of neoplasms.

The TP53 gene is called the guardian of the genome. Its mutations occur in a large percentage of tumors. They most often concern sequences that encode the DNA-binding domain (exons 5–8). The TP53 gene, together with the TP63 and TP73 genes, belongs to the oldest evolutionary family of cancer transformation suppressors. Its product, a full length p53 protein, consists of five domains and a flexible consolidator region and functions as a homotetramer. The regulation of p53 activity is caused by MDM2 protein, which contributes to proteasomal degradation of the suppressor.

This review deals with the most important aspects of the regulation of cell activity by p53 protein. It describes the structure of p53 protein and the associated therapeutic possibilities.