What does normal p53 protein do?
• The function of the p53 protein is to prevent cells with DNA damage from going through the cell cycle. • p53 protein binds in sequence specific manner to sites (p53-Response Elements) in certain genes (p53-Target Genes) such as WAF-1, BAX, MDM2 etc as a transcription factor. • Resulting regulatory protein checks the cell cycle and directly initiates DNA-damage repair or cell destruction (Apoptosis) based on the degree of DNA damage. Slide 3 What determines p53s affinity to the Target genes? • P53 binding sites (REs) in Target genes follow a general consensus sequence and are found to be very loose General consensus sequence: 5(Pu-Pu-Pu-C A/T T/A G-Py-Py-Py)3 Hypothesis: The degree of phosphorylation of the p53 protein modulates it affinity for the different p53-REs. Slide 4 Research design: To investigate patterns of phosphorylation as a possible factor behind p53 proteins’ Affinity to p53-REs in target genes, • The p53 protein would be made to bind to several of its target genes beg
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