PCL477H1 Study Guide - Final Guide: Sv40 Large T Antigen, Ribonucleotide Reductase, Dna-Binding Domain
9 Dec 2016
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Document Summary
Tumor suppressor normally mutated in cancer cells. Li-fraumeni syndrome: rare hereditary disorder linked to germ line mutations in p53. Usually 1 allele in germ line with compromised p53 (point mutations) Discovered: sv40 large t antigen protein produced from virus: when introduced to primary cells they behave like cancer cells, turns out this is an oncogene. Mutant p53 (missense) accumulates in cancer cells and increases sv40 protein production: cloned mutant versions of p53 introduced to normal cells become cancer cells, evidence of tumor suppressor gene. P53 can from tetramers and behave in a dominant negative fashion. Mutant protein (despite being 1 copy) can suppress wild type activity of p53. N-terminal: acidic transcriptional activation domain tells proteins to facilitate gene transcription. Central region: sequence-specific dna binding domain of protein (usually mutated in cancer cells: contains 6 mutational hot spots= 40% of p53 missense mutations. Oligermization domain: binds dna as a tetramer.
