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The interaction of p53 and MDM2 genes in cancers, in silico studies and phylogenetic analysis

Jayaraman A, Jamil K, Raju S

The normal cell cycle process is a crucial process and is generally mediated by a number of regulatory genes. One of the most important regulators is the tumor suppressor p53, which in turn is regulated by MDM2 gene. The expression of p53 and MDM2 is found to be frequently altered in many cancers and metastasis/ relapses .This is the first report to look at the evolutionary history of these genes to decipher the role of these genes in the tumorigenesis process using in silico methods. We also found that they showed high degree of sequence similarity across the mammalian species, indicating that these species probably share parallel cancer causing mechanisms. Their individual unrooted phylogenetic tree formed 5 clusters each; however, p53 gene was found in a large number of species whereas MDM2 was found in smaller number of species. The role of MDM2 is therefore limited and occurs in fewer species across the mammalian species. It is evident that these molecules play an important role in the cancer process, perhaps responsible for relapses and hence need to be explored further as therapeutic targets. Such studies that are based on evidence from paleontology and genetics suggest that mechanisms of cancer are embedded deeply throughout evolution. Understanding the phylogenetic evolution of these genes could help in furthering our knowledge on the mechanisms involved in cancer.