2004 Fiscal Year Final Research Report Summary
Molecular mechanism of transcriptional regulation of pyruvate kinase gene by glucose and insulin
| Project/Area Number |
14360074
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
食品科学・栄養科学
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| Research Institution | Nagoya University |
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Principal Investigator |
NOGUCHI Tamio Nagoya University, Graduate School of, Bioagriculutural Sciences, Professor, 大学院・生命農学研究科, 教授 (70135721)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Kazuya University of Fukui, Faculty of Medical Sciences, Associate Professor, 医学部, 助教授 (20263238)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Pyruvate kinase / Transcriptional regulation / Insulin / Glucose / Transcription factor / Protein interaction / Liver / Adipocytes |
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| Research Abstract |
1.SHARP2 was not involved in carbohydrate responsiveness of the L-type pyruvate kinase(LPK) gene, but its transcription was stimulated by insulin through phosphoinositide 3-kinase pathway in hepatocytes.
2.The LPK gene transcription in the liver was synergistically stimulated by NF1 family proteins bound to LII and LII', and HNF1α bound to LI. NF1 directly interacted with activation domain of HNF1α via its DNA binding domain, which resulted in stimulation of DNA binding activity of HNF1α.
3.A homeodomain protein Hex, which did not affect any activity of the LPK gene promoter directly, stimulated HNF1α activity by interacting with POU-homeodomain via its homeodomain. Thus, Hex stimulated transcription of the LPK gene through HNF1α.
4.It was suggested that ChREBP itself is involved in transcriptional regulation of the ChREBP gene by insulin/glucose. The rat ChREBP gene was isolated and its 5'-flanking region up to about 1000 bp was sequenced. The region similar to carbohydrate response element of the LPK gene was found in the upstream region, but it was not responsive to carbohydrate. In addition, we found that the gene contained sequences responsive to CREBP in the upstrem region.
5.Expression of the M2-type PK was regulated by insulin at both transcriptional and posttranscriptional levels. Insulin-responsive element was suggested to be present in the upstream region of the PKM gene from -0.5 kb to -2.2kb.
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