TY  - JOUR
AU  - Foroutan, Behzad
PY  - 2023
DA  - 2023/07/03
TI  - A Narrative Review of the <i>TP53</i> and Its Product the p53 Protein
JO  - OBM Genetics
SP  - 185
VL  - 07
IS  - 03
AB  - The main purpose of this paper was to generate a narrative review related to the current knowledge of the TP53 gene and its product, the p53 protein. It was also attempted to elucidate the different p53 reactivation strategies of great interest, as various small molecules are being studied to reactivate mutant p53. PubMed and ScienceDirect were searched for p53, mutant p53, and wild-type p53 limited by the title filter through the end of 2022. The collected articles were studied, evaluated and summarized. In the short (p) arm of chromosome 17, there is a special place for TP53. (17p.13.1). It is made up of 19,180 bp, which includes thirteen exons, (elevem exons, two alternative exons), and ten introns. TP53 is mutated in most types of human cancers resulting in aggressive cancer proliferation, immune system evasion, genomic instability, invasion, and metastasis. Under stress-free conditions, p53 function is negatively regulated by HDM2, a p53 target gene, which binds to it and establishes an auto-regulatory negative feedback loop that promotes proteasomal-dependent degradation. In these conditions, p53 maintains at low levels and normalizes biological operations as the master regulator of cell fate. However, under conditions of stress such as DNA damage, hypoxia, oxidative stress, oncogene expression, nutrient deprivation, ribosomal dysfunction, or telomere attrition the p53 selection pathway will be cell type-specific and depend on the type and severity of the cell damage. Post-translational modifications such as phosphorylation and acetylation, which induce the expression of p53 target genes, contribute to the p53 selection pathway. In these conditions, p53 tetramerized and stabilized in the nucleus and activated, and its levels increased in the cell due to blocking the interaction with MDM2. Valuable findings have been discovered that elucidate the biological, biochemical, immunological, physiological, and pathological roles of p53 and its fundamental roles in cancer biology and genetics. The information gathered here should contribute to a better understanding of the impact of p53 deregulation on cancer and new research aimed at finding new anticancer strategies capable of reactivating the cancer suppressive function of WT and/or blocking the function of mutant p53 in order to improve cancer therapy and prognosis.
SN  - 2577-5790
UR  - https://doi.org/10.21926/obm.genet.2302185
DO  - 10.21926/obm.genet.2302185
ID  - Foroutan2023
ER  -