The Guardian of The Genome: Suppression of Cancer - Dissertation Example

?p53 The Guardian Of The Genome Introduction This is the gene accorded the responsibility of coding proteins that often regulate the cycle of cells by first of all functioning to suppress cancer. Suppression of cancer is important in trying to combat the disease through acceptable medical interventions. The main reason why this gene is called the guardian is because it has a role in formulating stability through prevention of genome mutation. The name majorly rises from its molecular mass i.e. it is in a fraction totaling to 53 kilodalton of cell proteins. The history of the p53 states that it was first discovered in 1979 at Princeton University. The findings indicated possible initial existence as a target of the virus SV40. The strains witnessed during this periods induced tumor development. The gene was modified to be able to suppress the tumors and that version of the gene was revealed in 1989. This protein was honored by Science magazine in 1993. The ability to fight tumors really worked scientific wonder that was a scientific breakthrough. Scientific research had taken a new turn that could be associated with new findings The p53 gene is found on chromosome number seventeen on the human body. p53 is a phosphoprotein that has 393 amino acids. The protein has four domains namely: The unit which activates transcription factors The unit which identifies specific sequences of DNA. The unit responsible for protein tetramerization. The unit which identifies damaged DNA. It is important to note that if the p53 reaches defective levels, then it tends to allow deformed cells to penetrate, thereby resulting in cancer. The gene plays a vital role in apoptosis and cell cycle control. The levels of this protein are quite low in correctly working cells. The protein increase may be triggered greatly by DNA damage as well as other signals of stress. When the increase of p53 protein activity is triggered, they are required to participate in such activities as DNA repair, growth arrest and apoptosis. The concentration of p53 should by all means stay regulated. The proteins work well in suppressing tumors but in instances whereby they are not regulated, the proteins will speed up the aging process effected by excessive apoptosis. For the purpose of regulating the protein, Mdm2 is usually used so as to degenerate p53 through a system called ubiquitin. Roles of p53 include inducing apoptosis by binding Caspase to Apafl. This protein activates Bax, which then activates cytochrome c from the mitochondria found in the body. p53 regulates inhibitory expression of the proteins with the aim of inducing growth arrest. In case the p53 gene gets damaged, the ability to suppress tumor falls immensely. So that the humans who inherit just a single functional copy of the protein are mostly exposed to getting tumors at the early stages of their lives. They are likely to suffer from a syndrome called Li-Fraumeni. The p53 is also delicate as it can be easily damaged by mutagens in cells. This is mostly witnessed from the possibility that the cells start to exhibit uncontrolled division. Research shows that more than half of tumors experienced in humans occur due to deletion or mutation of the p53 gene. A therapeutic use of the p53 protein is when it’s introduced into cells that lack the protein so as to facilitate death of cells that cause cancer or to further prevent division. This is therefore one of the major reasons why hope is based on the successful performance of the proteins so as to be able do deal cancer a deathly blow. Cancer has had adverse effects on those affected such that lifestyle change is forced on them. Cancer gets difficult when detected at advances levels as treatment may become difficult therefore just necessitating control of spread of the effects of the deadly lifestyle disease. It is therefore important that the p53 genes stay within the human body system so as to avoid dealing with the outcome of reduced levels of p53 or even uncontrolled level that may go on to become fatal enough to speed up aging in humans. It is however unfortunate to note that some mutations that arise from these cancer cells may have adverse effects on the p53 proteins by impairing its ability to tame cancer, therefore, restoring the proteins in accurate quantities can be vital to be able to cure certain cancers. Research has shown that various studies carried out show that certain molecules were found to contain qualities that have the capability of restoring into p53 the activities that can suppress tumors in vitro. These molecules act to alter mutant conformation witnessed on p53 so as to restore the proteins back to their initial active forms. So far, it has yielded no great outcome the search for molecules that can induce biological responses, however, some active biological agents may be employed to do this job. A target that shows a promising form of active result in cancer treatment Molecular chaperone which, in combination with p53 can yield good result in vivo. Another virus that was initially viewed to propel cancer diseases has now been modified to assist in cancer therapy. Adenoviruses initially relied on host cells by secreting proteins so that they can replicate. ONYX-015 is the modified version of the adenovirus which multiplies in cancer cells that lack the p53. However, this modified version does not multiply in normal cells It reaches a point whereby suppression of p53 is important so as to facilitate replication of the virus. It was hoped by scientists that the said viruses could isolate tumor cells and still spread to different other surrounding tissues hence boosting efficacy and distribution. These cells replicated by the adenovirus ensure that the tumor dies. The scientists carried out lab tests on mice whereby the results were quite promising indeed. However, the clinical tests conducted on humans on the effective levels of ONYX-015. The results were inconclusive and only showed better results when combined with chemotherapy. E1B was discovered to exhibit many other functions that are quite important to the virus. The virus has often shown signs that it has the capability of replicating in certain cells that contain a wild type of the p53. There are extensive fibrotic tissues that were feared to cause the hardship witnessed in clinical testing as they hindered distribution of virus around the stubborn tumor.( Torgny, 2008) It is possible that the gene may get destroyed, then the ability to suppress the tumor often falls immensely due to the possibility that it happens that way. So that means that the humans who inherit just a single functional copy of the protein from parents or the environment are mostly exposed to getting tumors at the early stages of their lives as they commence adulthood. They are likely to suffer from a syndrome called Li-Fraumeni. The p53 is also delicate as it can be easily damaged by mutagens in cells. This is mostly witnessed from the possibility that the cells start to exhibit uncontrolled division. Research shows that more than half of tumors experienced in humans occur due to deletion or mutation of the p53 gene. The structure of the p53 is in a way that it is often composed of a pair of half sites that are linked by 0-13 nucleotide cluster. These two halves have copies of pentamer sequence. The structure of the p53 should therefore be critically scrutinized to ensure it has the right forms of acceptable structures that can assist it do the right job. Scientists should also ensure that humans have the right amount of this vital vitamin in their bodies so as to be able to fight the wrong cells in the body that can cause any form of cancer that can endanger the life of a patient. Studies conducted shown that various research carried out by experts in the field of Biology show that certain molecules were found to contain qualities that have the capability of restoring into p53 the activities that can suppress tumors in vitro. These molecules act to alter mutant conformation witnessed on p53 so as to restore the proteins back to their initial active forms. So far, it has yielded no great outcome the search for molecules that can induce biological responses, however, some active biological agents may be employed to do this job. A target that shows a promising form of active result in cancer treatment Molecular chaperone which, in combination with p53 can yield good result in vivo. These molecules should therefore be administered where necessary to boost the immune system so as to be able to fight dangerous cancer cells. (Franco, 2004) Research further shows that it was discovered that a mutant form of p53 was discovered to exist in more than half of all cancers. Tumor has the ability to develop without interference of the p53 as the accumulation of defective cells can alter the genetics in favor of such tumors that will take advantage of the inactive state of the p53 proteins. So in order to avoid giving good conditions for the thriving ability of these tumors, the p53 should be maintained in active levels that make individual patients strong enough to fight against insurgent cancer situations. The domains that make p53 relevant are the trans-activation called the N-terminal. This domain has two sub-domains of transcriptional activation. A proline-rich region that is adjacent that binds relevant domains to specific DNA sites that are targeted and the other terminals that are witnessed in regulated regions. These regulated domains are the ones that allow for stability and thus high affinity witnessed for DNA. The p53 has another different site that binds DNA which in turn links the regions that are regulated in the central domain. Therefore this goes on to delete mismatches in the DNAs (Pierre, 2013). A therapeutic use known all over the world by interested parties of the p53 protein is when it’s introduced into cells that lack the protein so as to facilitate death of cells that cause cancer or to further prevent division. This is therefore one of the major reasons why hope is based on the successful performance of the proteins so as to be able do deal cancer a deathly blow. Cancer has had adverse effects on those affected such that lifestyle change is forced on them. Cancer gets difficult when detected at advances levels as treatment may become difficult therefore just necessitating control of spread of the effects of the deadly lifestyle disease. It is therefore important that the p53 genes stay within the human body system so as to avoid dealing with the outcome of reduced levels of p53 or even uncontrolled level that may go on to become fatal enough to speed up aging in humans. The genes could be seen to mutate to facilitate a better understanding It is however unfortunate to note that some mutations that arise from these cancer cells may have adverse effects on the p53 proteins by impairing its ability to tame cancer, therefore, restoring the proteins in accurate quantities can be vital to be able to cure certain cancers (Alexander, 2006). Conclusion In summary, the protein has with it very good benefits that are vital for the research that stands out to assist in understanding cancer and cancer treatment. The p53 vitamin caries with it efforts to help people understand the reasons why cancer can be discovered early enough and how to facilitate its treatment. Doctors need the knowledge derived from the understanding that p53 has clinical values that have been proved to have many positive effects that can enable doctors to work the relevant information. Researchers in this field also need to be lauded for the combined knowledge arrived at. The study conducted also pays homage to the understanding of DNA structures as well as the science and more specifically the Biology that surrounds the rule of inheriting genes from parents or even getting genetic mutation that arises from the environment that an individual comes from. The p53 is a vital protein that remains important in daily life. Understanding all the important aspects that can in the long run work for the understanding of the importance of the p53 genome in fighting diseases like cancer and the importance of the protein in scientific undertakings. Bibliography Alexander Burkle 2006, Poly(adpribosyl)Ation. USA: Springer. Franco Cavalli, Heine Hoi Hansen, Stan B. Kaye 2004, Textbook of Medical Oncology Ed3. UK, Oxford: Taylor & Francis. P. David Josephy Professor of Molecular and Cellular Biology University of Guelph, Professor of Biochemistry Uppsala University Bengt Mannervik Karin and Herbert Jacobsson Chair 2006, Molecular Toxicology. Oxford: Oxford University Press. Pierre Hainaut 2013, p35 in the Clinics. France: Springer. Torgny Stigbrand, Jorgen Carlsson, Gregory P. Adams 2008, Targeted Radionuclide Tumor Therapy: Biological Aspects. Sweden: Springe. Read More