p53 tumor suppressor protein mutants R175H, G245S, R249S and R282W: structural prediction and analysis of full length proteins

Abstract

The tumor suppressor protein p53, the “Guardian of the Genome”1, prevents the development of cancerous tumors by removing or repairing cells with damaged genetic material. Approximately 50% or more of all human cancers are attributable to mutations in this protein.2,3 The p53 protein directs either of two major pathways through signaling for the DNA repair system, or, when the extent of damage is beyond repair, initiating programmed cell death, also known as apoptosis.4–12 When p53 itself becomes mutated, genetically compromised cells may be able to proliferate unchecked by p53 regulation which can lead to tumor proliferation. Knockout mice lacking p53 develop tumors when exposed to mutagens, suggesting the key role of p53 in tumor prevention.13–15