Hormonal Transcriptional Regulation of Phosphoenolpyruvate Carvoxykinase Gene
| Project/Area Number |
11671610
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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 |
Obstetrics and gynecology
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| Research Institution | Mie University |
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Principal Investigator |
YOKAWA Eiji (2000-2001) Mie University, Hospital, Assistant, 医学部・附属病院, 助手 (50240180)
杉山 隆 (1999) 三重大学, 医学部・附属病院, 助手 (10263005)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIYAMA Takashi Mie University, Hospital, Assistant, 医学部・附属病院, 助手 (10263005)
日下 秀人 三重大学, 医学部・附属病院, 助手
野田 和彦 三重大学, 医学部・附属病院, 助手 (10263013)
守屋 光彦 三重大学, 医学部・附属病院, 助手 (50314133)
陽川 英仁 三重大学, 医学部・附属病院, 助手 (50240180)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | PEPCK / GENE / TRANSCRIPTION / PREGNANCY / GLUCONEOGENESIS |
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| Research Abstract |
The phosphoenolpyruvate carboxykinase (PEPCK) gene promoter contains a glucocorticoid response unit (GRU) that includes three accessory factor binding sites (AF1, AF2 and AF3), two glucocorticoid receptor binding sites (GR1 and GR2) and a cAMP response element (CRE). All of these elements, and the proteins that bind to them, are required for a complete glucocorticoid response. The activation of the PEPCK gene in response to glucocorticoids requires a specific set of cis-acting elements that must be precisely positioned within the GRU. The distance between AF2 and GR1 is critical for the glucocorticoid response, while the distance and orientation requirements of AF1 and AF3 with respect to GR1 are more flexible. In addition, we showed that the GRU can act as a module, within a restricted region, in the context of the PEPCK promoter and in limited contexts of a heterologous promoter. These observations suggest that the structural requirement of the GRU exists, and this may have important
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implications for how multiple hormonal signals are integrated through a short segment of DNA.
Next, we identified activation domain of COUP-TF that binds to API and AF3 in the PEPCK gene promoter and serves as an accessory factor required for the complete induction of the PEPCK gene transcription by glucocorticoids. We showed that the C-terminal domain of COUP-TFI, located between amino acids 184-423, is involved in these three mechanisms of COUP-TFI activation. Furthermore, we show that COUP-TFI associates with GRIP1 and SRC-1 in vivo and that these coactivators potentiate the activity of COUP-TFI, suggesting that GRIP1 and SRC-1 are involved in the activation mechanism of COUP-TFI. The C-terminal 15 amino adds are required for the activation function of COUP-TFI and they are not required for the active repression by COUP-TFI. Then, over expression of coactivators does not convert a COUP-TFI repressor into a COUP-TFI activator.
Finally, we examined the involvement of PEPCK gene expression during pregnancy. mRNA levels of PEPCK did not change in pregnancy. Then, we are testing other enzymes that encode gluconeogenesis to assess further mechanism of carbohydrate metabolism in pregnancy. Less
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Report
(4 results)
Research Products
(4 results)
