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Structure And Function Of The P53 As A Tumor Suppressor Research Paper

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Tumor Suppressor p53 The p53 tumor suppressor, also known as the TP 53 or tumor protein can be referred to as a gene that codes for a protein that is responsible for the regulation of the cycle of the cell and therefore acting as tumor suppression. It is significant for cells in multicellular organisms to suppress cancer, p53 has been referred to as ‘the guardian of the genome’ as extracted from its role in the conservation of the stability by hindering the mutation of the genome. The name p53 comes from the molecular mass that it has-53 kilodalton fraction of the cell proteins.

The research conceited with the cure for cancer and its management dates many decades ago, but in 1979 there was a significant breakthrough. There were six groups of investigators each working separately and independent of each other came to an amazing similar discovery of a 53 kDa protein that was seen to be inherent in the mouse cells and the human cells. Among these studies, five of them discovered the protein because it was bound to the T-antigen in SV40 infected cells hence was immunoprecipitated with antibodies secreted against the viral protein. It was also discovered that the same protein was serendipitous when an antiserum generated against a chemically induced mouse sarcoma was seen to react with a 53 kDa protein present in transformed buy not normal mouse cells. Among the noted researchers noted are Arnold Levine, William Old and David Lane who identified the p53 identified it while working at Princeton University, Sloan-Ketterin Memorial Hospital and Dundee University (UK) respectively. Before then, it had been hypothesized to be in existence as the target of the SV 40, which was a strain that initiated development of tumors. Initially, it was thought to be an encogene but the true characteristics as a tumor suppressor gene was revealed in 1989. Come 1993, the p53 was historically voted as the molecule of the year by the science magazine, making it a great breakthrough in the cancer management globally (Nature Education, 2014).

The p53 structure

The p53 is widely known to be a phosphoprotein that is composed of 393 amino acids, it has four units otherwise referred to as domains. These four domains are; the domain that recognizes specific DNA sequences (core domain), the domain that activates transcription factors, the domain that takes care of the tretramerization of the protein and lastly the domain that recognize damaged DNA like the misaligned base pairs or single-stranded DNA. The wild-type p53 is categorized...

It is noted that the defective p53 can facilitate the abnormal cells proliferation, resulting in cancer. It is also noted that a significant number of human tumors, indeed 50% of all human tumors contain p53 mutants. The evolution and change of a normal cell to cancerous cells is explained t be a complex process with various steps involving genetic and epigenetic alterations that give selective advantages on the altered cells. The tumerigenesis alterations are seen to give the evolving tumor with self-sufficiency of growth signals, evasion from programmed cell death, insensitivity to antigrowth signals, sustained angiogenesis, unlimited replicative potential and also the ability to invade the metastasize (Freed-Pastor W.A. & Prives C., 2017).
Though there has been massive research put into the research on the understanding of the cancer cells, though there have been impressive progress on the same over the past few decades, the full molecular understanding of the cancer still remains a big challenge to the biomedical community. In normal cells, the p53 protein level is known to be low, the DNA damage and other accompanying stress signals may activate the multiplication of p53 proteins and these p53 increased proteins have three main functions-to repair the DNA, growth arrest and apoptosis/cell death. The cell cycle progression is stopped by the growth arrest in effect hindering the replication of the damaged DNA. In the process of the growth arrest, the p53 may trigger the transcription of the proteins involved in DNA repair. Apoptosis is considered as the last resort which is meant to stop or prevent the proliferation of cells containing abnormal DNA.

It is important to note that the cellular concentration of p53 needs to be closely and tightly regulated since in as much as it can suppress the tumors, high levels of p53 may hasten the aging process by excessive apoptosis. Mdm2 is known to be one of the most effective regulators which is able to initiate the degradation of p53 through the system known as ubiquitin system. The regulation mechanism is illustrated in the below figure.

Mdm2 regulation mechanism as illustrated by Bioinformatics (2017)

There are target genes that the p53 target in hindering the cancer growth. P53 is said to be a transcriptional activator that regulate the…

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References

Bioinformatics (2017). Primary Information of p53. Retrieved November 24, 2017 from http://www.bioinformatics.org/p53/introduction.html

Hollstein M. and Harris C.C., (1993). Clinical Implications of the p53 Tumor-Suppressor Gene. Retrieved November 23, 2017 from http://www.nejm.org/doi/full/10.1056/NEJM199310283291807

Freed-Pastor W.A. & Prives C., (2017). Mutant p53: one name, many proteins. Retrieved November 23, 2017 from http://genesdev.cshlp.org/content/26/12/1268.full

Nature Education, (2014). p53 : The Most Frequently Altered Gene in Human Cancers. Retrieved November 24, 2017 from https://www.nature.com/scitable/topicpage/p53-the-most-frequently-altered-gene-in-14192717


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