Editorial: Mutant p53 in Cancer Progression and Personalized Therapeutic Treatments
Oleg Timofeev
Abstract
The p53 tumor suppressor is a transcriptional factor that controls a network of cellular processes essential for the maintenance of genomic integrity and prevention of malignant transformation. Ironically, p53 was initially described as an oncogene, and it took quite some time to realize that the protein found in tumors was a mutated version. Mutations in the TP53 gene are the most frequent genetic alterations detected in human cancers. In contrast to other tumor suppressors that are usually inactivated by frame-shift or nonsense mutations, the majority of cancer-associated TP53 mutations are non-synonymous missense substitutions, which indicate that cancer cells can benefit from the presence of mutated p53 protein with compromised functions (loss of function -LOF). Furthermore, some common TP53 missense mutations possess gain-of-function (GOF) properties that furnish mutant protein with new oncogenic qualities. A plethora of mutations detected in the TP53 gene, which gives rise to more than 2000 different protein variants, makes the issue very complex, but the progress in experimental and data mining methods provided significant advances in understanding functional consequences of different p53 mutations.