Lecture 10a revised to post [Compatibility Mode]

Lecture 10a revised to post [Compatibility Mode] - Lecture...

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ecture 10- verview Lecture 10 Overview p53: the master regulator • history of p53 • how is p53 activated how is p53 inactivated • role as a transcription factor G1 arrest G arrest G2/M arrest replication blockade regulation of extrinsic apoptotic signaling regulation of intrinsic apoptotic signaling ew members of the p53 gene family new members of the p53 gene family
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the history of p53 • originally identified in 1979 as a cellular protein that bound to the simian virus SV40 large T antigen • protein found to accumulate in nuclei of cancer cells gene cloned from rodent and human cancer cells • when gene overexpressed in normal rodent cells – oncogenic activity •i late 1980s, scientists discovered that they were n late 980s, sc ent sts d scovered that they were studying mutant versions of the p53 gene that contained missense mutations, instead of the wild- type gene • ability of p53 to form tetramers: protein could behave in a dominant-negative fashion: allele- producing mutant p53 could suppress the activity of wild-type p53
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‘history wheel’ of p53 Wild-type or normal p53 now considered to be a tumour suppressor gene and a ‘guardian of the genome’ Li-Fraumeni syndrome is a rare hereditary disorder linked to germline mutations in in p53 –syndrome greatly increases risk of developing cancers, (particularly breast cancer, brain tumours, acute leukemias, sarcomas)
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p53 protein domains N-terminal (orange) domain :
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Lecture 10a revised to post [Compatibility Mode] - Lecture...

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