A new mouse model, created by scientists at the Salk Institute for Biological Studies, suggests that what researchers have learned about the regulation of p53 activity from in vitro studies may not be relevant to living, breathing organisms. The Salk scientists' findings are published in this week's online early edition of the journal Proceedings of the National Academy of Sciences.
Until now, scientists had assumed, based on studies in cultured cells, that p53 had to be modified by attaching chemical groups to specific sites on the protein to function normally in the body. The new research indicates that these modifications are not necessary to activate p53 under conditions of stress or to prevent p53 from throwing a wrench into the cell cycle machinery, when nothing is wrong.
"The chemical modifications of the p53 protein that we thought were essential for its normal function may just fine-tune the activity of the protein under physiological conditions in a living organism, but they are not essential," explains lead investigator professor Geoffrey M. Wahl. "This new study focuses our attention on the network of regulators of p53 and how they are regulated."
"This study caused a big shift in how we think about p53," explains Salk scientist and first author Kurt Krummel. "You have to look at all interacting partners because after all, modifications of p53 itself might not be so important as modifications of negative regulators and co-activat