Molecular Biotech 472
May 22, 2019
p53 also described as tumor protein or TP53 is a gene which codes for a protein that regulates the cell cycle thus functions as a tumor suppression. P53 is very essential for cells in the body to suppress cancer. It has been described as “the genome guardian’’, referring to its role in maintaining stability through the prevention of genome mutation. The name p53 is derived from its molecular mass, which is 53 kilodalton fraction of cell proteins. P53 gene is situated on the seventeenth chromosome (Muller & Karen 17).
The p53 protein is a phosphor-protein comprising of 393 amino acids. It is made up of four distinct domains or units: a domain or unit that activates transcription factors, a domain that recognizes particular DNA sequences, a domain that is responsible for protein tetramerization, and a domain that recognizes damaged DNA including single-stranded DNA or misaligned base pairs. The impairment of p53 gene is associated with reduced tumor suppression. Individuals who inherit just one functional p53 copy are at higher risks of developing tumors in early adulthood, a condition termed as Li-Fraumeni syndrome (Muller & Karen 17). Mutagens ( viruses, radiations, or chemicals) can also damage p53 increasing the chances that the cell will start the uncontrolled division. Over half of human tumors contain a deletion or mutation of the p53 gene (Muller & Karen 18).
In health, p53 is constantly manufactured as well as degraded in the cell. The degradation of p53 is related to MDM-2 binding. A negative feedback loop, P53 induces MDM-2. But mutant p53s usually do not include MDM-2 and are therefore van accumulate as extreme high concentration. Mutant p53 protein can also inhibit normal production of p53 protein (Kim et al. 5).
Tumor suppressor p53 plays a key role in suppressing tumor. P53 is one of most often-mutated genes in cancer (Vincek et al 2). As a transcription factor, p53 usually exerts its role in the suppression of tumor by transcriptional regulation of its downstream target genes (Aubrey et al 2). The tumor suppressor protein, p53 usually responds to cellular stress including damage of the DNA, oncogenic activation and hypoxia through the transactivation of the downstream genes associated with DNA repair, apoptosis, cell cycle arrest, senescence, and the progression of the cell cycle (Kim et al. 5). However, the latest trends reveal that p53 usually plays complex roles in the regulation of glucose metabolism. P53 promotes oxidative phosphorylation, suppresses glycolysis at multiple stages and controlling glutamine as well as lipid metabolism (Rivlin et al. 74). P53 actions have also been associated with influencing Warburg Effect that is characteristic of cancer cells (Rivlin et al. 74).
P53 has been indicated to repress glycolysis via multiple methods. Glucose transportation across the plasma membrane of cells is usually the initial rate-limiting phase for the...