Akt-mediated Regulation of Notch-dependent Transcription

Abstract

We have investigated the effect of Akt/PKB on Notch Intracellular Domain (NICD)-mediated transcription. The transient transfection studies using both 293T and Cos-7 cells revealed that myristylated constitutive active Akt could down-regulate NICD-dependent transcription in both cell lines. When the intracellular localization of myc-tagged NICD was investigated, all three Akt isoforms effectively inhibited proper nuclear localization of NICD. Akt2 could also down-regulate protein level of myc-NICD, suggesting that protein degradation process(es) might be involved in down-regulation of NICD-dependent transcription by Akt2. Studies using kinase-dead dominant negative Akt (K179M) showed that Akt kinase activity is responsible for down-regulation of NICD-dependent transcription. These results may suggest possible regulation of NICD transcription activity by Akt-mediated phosphorylation