title: PI3K regulates BMAL1/CLOCK-mediated circadian transcription from the Dbp promoter.
abstract: The circadian rhythm generated by circadian clock underlies a molecular mechanism of rhythmic transcriptional regulation by transcription factor BMAL1/CLOCK. Importantly, the circadian clock is coordinated by exogenous cues to accommodate to changes in the external environment. However, the molecular mechanisms by which intracellular-signaling pathways mediate the adjustments of the circadian transcriptional rhythms remain unclear. In this study, we found that pharmacological inhibition or shRNA-mediated knockdown of phosphatidylinositol 3-kinase (PI3K) blocked upregulation of Dbp mRNA induced by serum shock in NIH 3T3 cells. Moreover, the inhibition of PI3K significantly reduced the promoter activity of the Dbp gene, as well as decreased the recruitment of BMAL1/CLOCK to the E-box in the Dbp promoter. Interestingly, the inhibition of PI3K blocked heterodimerization of BMAL1 and CLOCK. Our findings suggest that PI3K signaling plays a modulatory role in the regulation of the transcriptional rhythm of the Dbp gene by targeting BMAL1 and CLOCK.
authors.affiliation: a Faculty of Applied Bioscience, Department of Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Morishita
authors.affiliation: a Faculty of Applied Bioscience, Department of Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Miura
authors.affiliation: a Faculty of Applied Bioscience, Department of Bioscience , Tokyo University of Agriculture , Tokyo , Japan.|b Core Research for Evolutional Science and Technology, Japan Science and Technology Agency , Saitama , Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kida
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics* / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D057906:Circadian Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic; D055503:Protein Multimerization; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D002867:Chromones; D004268:DNA-Binding Proteins; C498260:Dbp protein, mouse; D009025:Morpholines; D034741:RNA, Small Interfering; D014157:Transcription Factors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D056926:CLOCK Proteins; C538944:Clock protein, mouse; C509622:1-phosphatidylinositol 3-kinase p110 subunit, mouse; D058534:Class I Phosphatidylinositol 3-Kinases
keywords: BMAL1; CLOCK; Dbp; PI3K; circadian clock