Fe65 Ser228 is Phosphorylated by ATM/ATR and Inhibits Fe65-APP-Mediated Gene Transcription

In this study, we identified Fe65 Ser228 as a novel target of the ATM and ATR protein kinases, in a reaction that occurred independently of APP. Neither phosphorylation nor mutation of Ser228 affected the Fe65-APP protein complex, though this was markedly decreased after UV treatment, with a concomitant decrease in the protein levels of APP in cells. Finally, mutation of Ser228 to Ala (thus blocking phosphorylation) caused a significant increase in Fe65-APP transcriptional activity, whereas phosphomimetic mutants (S228D and S228E) showed decreased transcriptional activity. These studies identify a novel phosphorylation site within Fe65 and a novel regulatory mechanism for the transcriptional activity of the Fe65-APP complex.
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Cell Source Type: research