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Publication : Down-regulation of Notch-dependent transcription by Akt in vitro.

First Author  Song J Year  2008
Journal  FEBS Lett Volume  582
Issue  12 Pages  1693-9
PubMed ID  18440314 Mgi Jnum  J:136247
Mgi Id  MGI:3795790 Doi  10.1016/j.febslet.2008.04.024
Citation  Song J, et al. (2008) Down-regulation of Notch-dependent transcription by Akt in vitro. FEBS Lett 582(12):1693-9
abstractText  The effect of Akt on Notch intracellular domain (NICD)-mediated transcription was investigated. Transfection experiments revealed that constitutively active Akt down-regulates NICD-dependent transcription. Kinase inactive dominant negative Akt did not affect NICD transcriptional activity, indicating that Akt kinase activity is responsible for the down-regulation. Studies using histone deacetylase (HDAC) and silencing mediator of retinoid and thyroid hormone receptor (SMRT) revealed that modulation of NICD transcriptional activity is not mediated by an HDAC-dependent mechanism or recruitment of the co-repressor SMRT. Akt inhibited proper nuclear localization of NICD, and phosphorylated NICD both in vitro and caused its hyperphosphorylation in vivo. These results may suggest possible regulation of NICD transcriptional activity by Akt-mediated phosphorylation and subsequent inhibition of proper nuclear localization of NICD.
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