The p53 gene

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The p53 gene may be the most important gene preventing human cancer. This gene is mutated in about half of all cancers (and the pathway in which it participates is mutated in essentially all cancers). A. We can envisage two mechanisms to increase the amount of p53 protein when it is suddenly needed. First,transcription and translation of the p53 gene might be low in the absence of a stimulus and markedly increased after stimulation. Second, transcription and translation of the p53 gene might be high at all times, but the protein amount is normally low as a result of proteolytic degradation; after stimulation, degradation is inhibited and consequently the protein amount increases. The latter mechanism is actually used by cells. Suggest the most important advantage of this mechanism.B. List two of the four major classes of stimuli that evoke increased p53 amounts in normal human cells.C. A defect in p53 increases the likelihood of amplification of proto-oncogenes and loss of tumor suppressor genes. Describe the two ways in which p53 normally works to prevent these outcomes. Describe the sequence of steps that can lead to these outcomes in the absence of p53.

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