Down-regulation of Notch-dependent transcription by Akt in vitro.
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.
Song
Jieun
J
Department of Life Science, College of Natural Science, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Republic of Korea.
Park
Sungwoo
S
Kim
Minsoon
M
Shin
Incheol
I
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D056985:Nuclear Receptor Co-Repressor 2; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D007527:Isoenzymes; C539130:NCOR2 protein, human; D056985:Nuclear Receptor Co-Repressor 2; D051880:Receptors, Notch; D012097:Repressor Proteins; D051057:Proto-Oncogene Proteins c-akt; D006655:Histone Deacetylases