2001 Fiscal Year Final Research Report Summary
Role of poly ADP polymerase in transcriptional regulation by nuclear receptor
| Project/Area Number |
11671083
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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 |
Endocrinology
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| Research Institution | Shinshu University |
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Principal Investigator |
MIYAMOTO Takahide Shinshu Univ., Dept of Geriatrics, Lecturer, 医学部, 講師 (20192768)
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| Co-Investigator(Kenkyū-buntansha) |
ICHIKAWA Kazuo Shinshu Univ., Dept of Geriatrics, Lecturer, 医学部, 講師 (40159835)
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| Project Period (FY) |
1999 – 2001
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| Keywords | Nuclear receptor / Transcription / poly( ADP-ribose ) polymerase / Interaction |
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| Research Abstract |
Mammalian poly( ADP-ribose ) polymerase ( PARP ) is a nuclear chromatin-associated protein with molecular mass of 114 kDa that catalyzes the transfer of ADP-ribose units from NAD+ to nuclear proteins that are located within the chromatin. We report here the identification of a novel property of PARP as a modulator of nuclear receptor signalling. PARP directly bound to the retinoid X receptors ( RXR ) and repressed the ligand-dependent transcriptional activities mediated by the heterodimers of RXR and the thyroid hormone receptor ( TR ). The interacting surface is located in the DNA binding domain of RXRa. The gel shift assay demonstrated that PARP bound to the TR/RXR heterodimers on the response element. Overexpression of the wild-type PARP selectively blocked the nuclear receptor function in the transient transfection experiments, while the enzyme defective mutant PARP did not show significant inhibition, suggesting that the essential role of poly ADP-ribosyl enzymatic activity in the gene regulation by nuclear receptors, Furthermore the PARP fused to Gal4 DNA binding domain suppressed the transcriptional activity of promoter harboring Gal4 binding site. Thus the PARP has transcriptional represser activity when recruited to the promoter. These results indicates that poly ADP-ribosylation is a negative co factor in gene transcription, regulating the member of the nuclear receptor superfamily.
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