The Importance of Cysteine Residues in p53 Function

Speaker: Wendy Evans

Abstract: The tumor suppressor protein p53 requires thioredoxin reductase in order to stimulate reporter gene expression in yeast. This suggests that p53 contains one or more cysteine residues that make the protein prone to oxidative inactivation. Replacement of each individual cysteine in p53 with the structurally similar but non-oxidizable amino acid serine did not relieve dependence on thioredoxin reductase. This suggested that more than one cysteine may be involved. To address this possibility, mutant constructs of p53 with multiple cysteine to serine mutations were constructed and will be tested for reporter gene activation in TRR1 and (trr1 cells. The results will establish whether an oxidation-resistant p53 protein can be derived by replacing multiple cysteines.