PI3K regulates BMAL1/CLOCK-mediated circadian transcription from the Dbp promoter
| Autor: | Satoshi Kida, Yoshikazu Morishita, Daiki Miura |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Transcription Genetic Class I Phosphatidylinositol 3-Kinases Morpholines Circadian clock CLOCK Proteins E-box Biology Applied Microbiology and Biotechnology Biochemistry RAR-related orphan receptor alpha Analytical Chemistry Mice 03 medical and health sciences 0302 clinical medicine Circadian Clocks Internal medicine medicine Transcriptional regulation Animals Circadian rhythm RNA Small Interfering Promoter Regions Genetic Molecular Biology ARNTL Transcription Factors Organic Chemistry General Medicine Circadian Rhythm DNA-Binding Proteins CLOCK 030104 developmental biology Endocrinology Gene Expression Regulation Chromones NIH 3T3 Cells Protein Multimerization 030217 neurology & neurosurgery Signal Transduction Transcription Factors Biotechnology |
| Zdroj: | Bioscience, Biotechnology, and Biochemistry. 80:1131-1140 |
| ISSN: | 1347-6947 0916-8451 |
| DOI: | 10.1080/09168451.2015.1136885 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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