p53 Tumor Suppressor: Functional Regulation and Role in Gene Therapy

Abstract

p53, a homo-tetrameric protein found in mammalian cells, derives its name from the fact that it settles at around 53KDa position in SDS-PAGE, due to a “kink” in its structure. In its functional state, p53 forms a homo-tetramer and binds to the promoters of a wide array of genes. Binding of p53 downregulates the transcription of target genes. Most of the gene targets of p53 are involved in cell cycle progression, and therefore, any malfunctions associated with p53 have catastrophic consequences for the cell. The gene encoding for p53 known as TP53 is the most well-studied gene in the entire genome because of being the most highly mutated gene in all cancer types. It is due to this widely accepted and documented “cell protective feature” that p53 is generally referred to as “the guardian of the genome.” In this chapter, we will discuss the involvement of p53 in relation to carcinogenesis. We will also cover the major functions of p53 under normal conditions, major mutations of the TP53 gene, and their association with different forms of cancer.