Molecular mechanism of the transcription regulation by the retinoic acid receptor in human salivary gland cell line HSG.
| Project/Area Number |
11671850
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Iwate Medical University |
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Principal Investigator |
KYAKUMOTO Seiko Iwate Medical University, School of Dentistry, Assistant professor, 歯学部, 講師 (90118274)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAI Masazumi Iwate Medical University, School of Dentistry, Research associate, 歯学部, 助手 (00217960)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | retinoic acid / retinoic acid receptor / coactivator / corepressor / COUP-TF / histone acetyltransferase / salivary gland cell line / CBP / ヒストンアセチル化酵素 |
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| Research Abstract |
Growth of HSG cells is regulated by retinoic acid (RA). Recently, it has been revealed that, in the process of RA signaling, retinoic acid receptors (RAR) interact with coactivators such as CREB-binding protein (CBP) and p160 family member proteins, which facilitates the access of core transcription factors to the DNA.To investigate the relationship of coactivators to the RA signaling in HSG cells, we examined the expression of coactivators. Immunoprecipitation and western blotting revealed the expression of CBP and steroid receptor coactivator 1 (SRC 1), which exhibited the activity of histone acetyltransferase. The overexpression of CBP in HSG cell strongly increased the RA-dependent transcription activation approximately 10-fold. This increase of the transactivation was inhibited by the transfection of the antisense oligonucleotide for CBP.These findings suggest that CBP expressed in HSG cells mediates the growth-regulating transcription activation in concert with RARs.
We have previously cloned the DNA fragment of COUP-transcription factor I (COUP-TFI). In this study, the expression of full length COUP-TFI was confirmed by use of RT-PCR and western blotting. To determine the role of COUP-TFI in the RA signaling, the reporter gene analysis was examined. The overexpression of COUP-TFI suppressed the RA-induced transcription activation of the reporter gene. Similar results were shown using a chromatin-integrated stably-transfected reporter gene system. The antisense oligonucleotide for COUP-TFI squelched the RA-dependent growth inhibition which was measured by the [^3H]thymidine incorporation. From these results, COUP-TFI very likely regulates RA-sensitive processes such as proliferation or differentiation of the cells by repressing the RA-induced transactivation.
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Report
(3 results)
Research Products
(14 results)
