P53

Abstract

Since its discovery 15 years ago, the p53 gene and its protein products have been the subjects of an almost unprecedented investigation. Justification for this lies in the critical role p53 plays as one of the cell cycle check points that control proliferation and differentiation. P53 is a tumor-suppressor gene found on chromosome 17p, and alterations (mussense mutation or deletion) within the coding sequences of gene are among the most frequent genetic changes detected in human neoplasnis. Mutation usually teads to the loss of DNA binding and transcriptional regulatory regulatory activities of the p53 nuclear phosphoprotein, with a corresponding loss of its growth suppressive activity. The tumor suppressor function of the normal gene and its wild-type (wt) p53 protein is replaced by the mutant form's oncognic properties. The mutated product of p53 is a protein with abnormal conformation, impaired DNA-binding, and a prolonged (stabilized) half-life, the latter of which results in Immunohistochemically detectable levels within nuclei in nearly all neoplasms showing p53 gene mutatin. Mutations of p53 or a complete loss of the gene is one of the important causes of failure to prevent cells from entering the S-phase of the cell cycle and malignancy. As more basic imformation of the molecular functions and cellular interactions of p53 accrues, it becomes evident that the genetic complexity of the gene and its protein products render simplistic clinical interpretations untenable. This ia especially true for prognostic or predictive screenings. Nonetheless, analysis of p53 in neoplastic or predictive states is a powerful molecular tool for dissecting the oncogenic process. In this review, we offer a contemporary assessment of the basic science and clinical status of p53.