1998 Fiscal Year Final Research Report Summary
Functional analysis of coactivators acting on Arnt.
| Project/Area Number |
09680610
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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 biochemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
SOGAWA Kazuhiro Tohoku University, Graduate School of Science, Department of Chemistry, Associate Professor, 大学院・理学研究科, 助教授 (80175421)
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| Project Period (FY) |
1997 – 1998
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| Keywords | transcription factor / PAS domain / xenobiotics / EIA / Ah receptor |
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| Research Abstract |
Arnt is a transcription factor which forms a heterodimer with the Ah receptor (AhR)activated with xenobiotics such as 3-methylchoranthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. This liganded-AhR/Arnt complex bounds XRE (xenobiotic response element) which localizes upstream region of MC-inducible genes. It was reported that El A, an early gene product of adenovirus, inhibits the indelible transcription strongly. However, the mechanism of the inhibition remained unclear. Recently, in some transcriptional inhibition of genes by ElA it become clear thatCBP/P300 is involved in the inhibition. We hypothesized that transcription by AhR/Arntcomplex is also mediated through CBP/p300. Protein-protein interactions between Arnt activation domain located in the C-terminus and CBP/p300 was investigated in the two hybrid system in yeast and cultured cells. Both results showed that there is an interaction between them. In contrast, activation domain of the AhR showed no interaction withCBP/p300. Binding regions in CBP/p300 to Arnt activation domain were examined. Finally, it was found that CREB-binding domain of CBP/p300 was responsible for the interaction. Several issues remains unsolved. What coactivator mediates activity of AhR activation domain. Whether or not ElA could suppress the transcriptional activity of heterodimers such as Arnt/Sim, and Arnt/HIF-la.
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