2005 Fiscal Year Final Research Report Summary
Individual differences of the regulation mechanism of the human carboxylesterase gene
| Project/Area Number |
16590081
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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 |
Drug development chemistry
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| Research Institution | Chiba Institute of Science (2005)
Chiba University (2004) |
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Principal Investigator |
HOSOKAWA Masakiyo Chiba Institute of Science, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (70181500)
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| Project Period (FY) |
2004 – 2005
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| Keywords | carboxylesterase / regulation mechanism / Sp1 / C / EBP / promoter / human liver / individual differences |
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| Research Abstract |
Mammalian carboxylesterase (CES) comprise a multigene family, which gene products are localized in the endoplasmic reticulum. We have recently described that major forms of CES in the human liver termed CES HU1 belongs to the CES1 family and that it is thought to play an important roles in drug and lipid metabolism. Since the expression level of CES HU1 may affect the level of drugs and lipid, it is important to understand the mechanism by which CES HU1 gene expression is regulated. In this study, we isolated the two CES genes encoding human CES HU1, which were tentatively designated as CES HU1a and CES HU1b. Both genes exist in inverted duplication on chromosome 16. These genes were completely similar, except for exon 1 and putative cis elements. The transcriptional level of CES HU1a was much higher than CES HU1b in human livers. Results of deletion assays and electrophoretic mobility shift assays suggested that the region from -160 to +54 consisted of the both gene promoters. However, Sp1 and C/EBP interacted with the CES HU1 a promoter, but not CES HUM promoter. It was concluded that these two genes most probably arose from an early gene duplication event and that their highly conserved structures and difference in regulation at the transcriptional level argue strongly for a significant role for each gene product in cellular metabolism.
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[Journal Article] Allelic expression imbalance of the human CYP3A4 gene and individual phenotypic status.2004
Author(s)
Hirota T, Ieiri I, Takane H, Maegawa S, Hosokawa M, Kobayashi K, Chiba K, Nanba E, Oshimura M, Sato T, Higuchi S, Otsubo K.
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Journal Title
Hum Mol Genet. 13(23):
Pages: 2959-2969
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Allelic expression imbalance of the human CYP3A4 gene and individual phenotypic status.2004
Author(s)
Hirota T, Ieiri I, Takane H, Maegawa S, Hosokawa M, Kobayashi K, Chiba K, Nanba E, Oshimura M, Sato T, Higuchi S, Otsubo K.
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Journal Title
Hum Mol Genet. 13(23)
Pages: 2959-2969
Description
「研究成果報告書概要(欧文)」より
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