This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Miyamoto, T.
Right arrow Articles by Hashizume, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Miyamoto, T.
Right arrow Articles by Hashizume, K.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 1999, p. 2644-2649, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Inhibition of Nuclear Receptor Signalling by Poly(ADP-Ribose) Polymerase

Takahide Miyamoto,* Tomoko Kakizawa, and Kiyoshi Hashizume

Department of Geriatrics, Endocrinology and Metabolism, Shinshu University School of Medicine, Matsumoto 390-8621, Japan

Received 19 November 1998/Returned for modification 4 January 1999/Accepted 12 January 1999

Mammalian poly(ADP-ribose) polymerase (PARP) is a nuclear chromatin-associated protein with a molecular mass of 114 kDa that catalyzes the transfer of ADP-ribose units from NAD+ to nuclear proteins that are located within chromatin. We report here the identification of a novel property of PARP as a modulator of nuclear receptor signalling. PARP bound directly to retinoid X receptors (RXR) and repressed ligand-dependent transcriptional activities mediated by heterodimers of RXR and thyroid hormone receptor (TR). The interacting surface is located in the DNA binding domain of RXRalpha . Gel shift assays demonstrated that PARP bound to TR-RXR heterodimers on the response element. Overexpression of wild-type PARP selectively blocked nuclear receptor function in transient transfection experiments, while enzyme-defective mutant PARP did not show significant inhibition, suggesting that the essential role of poly(ADP-ribosyl) enzymatic activity is in gene regulation by nuclear receptors. Furthermore, PARP fused to the Gal4 DNA binding domain suppressed the transcriptional activity of the promoter harboring the Gal4 binding site. Thus, PARP has transcriptional repressor activity when recruited to the promoter. These results indicates that poly(ADP-ribosyl)ation is a negative cofactor in gene transcription, regulating a member of the nuclear receptor superfamily.

* Corresponding author. Mailing address: Department of Geriatrics, Endocrinology and Metabolism, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. Phone: 81-263-37-2686. Fax: 81-263-37-2710. E-mail: miyamoto{at}hsp.md.shinshu-u.ac.jp.

Molecular and Cellular Biology, April 1999, p. 2644-2649, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Frizzell, K. M., Gamble, M. J., Berrocal, J. G., Zhang, T., Krishnakumar, R., Cen, Y., Sauve, A. A., Kraus, W. L. (2009). Global Analysis of Transcriptional Regulation by Poly(ADP-ribose) Polymerase-1 and Poly(ADP-ribose) Glycohydrolase in MCF-7 Human Breast Cancer Cells. J. Biol. Chem. 284: 33926-33938 [Abstract] [Full Text]  
  • Ono, T., Kaneda, T., Muto, A., Yoshida, T. (2009). Positive Transcriptional Regulation of the Human {micro} Opioid Receptor Gene by Poly(ADP-ribose) Polymerase-1 and Increase of Its DNA Binding Affinity Based on Polymorphism of G-172 -> T. J. Biol. Chem. 284: 20175-20183 [Abstract] [Full Text]  
  • Huang, D., Yang, C., Wang, Y., Liao, Y., Huang, K. (2009). PARP-1 suppresses adiponectin expression through poly(ADP-ribosyl)ation of PPAR{gamma} in cardiac fibroblasts. Cardiovasc Res 81: 98-107 [Abstract] [Full Text]  
  • Wang, J., Bian, C., Li, J., Couch, F. J., Wu, K., Zhao, R. C. (2008). Poly(ADP-ribose) Polymerase-1 Down-regulates BRCA2 Expression through the BRCA2 Promoter. J. Biol. Chem. 283: 36249-36256 [Abstract] [Full Text]  
  • Di Palma, T., de Cristofaro, T., D'Ambrosio, C., Del Prete, D., Scaloni, A., Zannini, M. (2008). Poly(ADP-ribose) polymerase 1 binds to Pax8 and inhibits its transcriptional activity. J Mol Endocrinol 41: 379-388 [Abstract] [Full Text]  
  • Bai, P., Houten, S. M., Huber, A., Schreiber, V., Watanabe, M., Kiss, B., de Murcia, G., Auwerx, J., Murcia, J. M.-d. (2007). Peroxisome Proliferator-activated Receptor (PPAR)-2 Controls Adipocyte Differentiation and Adipose Tissue Function through the Regulation of the Activity of the Retinoid X Receptor/PPAR{gamma} Heterodimer. J. Biol. Chem. 282: 37738-37746 [Abstract] [Full Text]  
  • Jeyakumar, M., Liu, X.-f., Erdjument-Bromage, H., Tempst, P., Bagchi, M. K. (2007). Phosphorylation of Thyroid Hormone Receptor-associated Nuclear Receptor Corepressor Holocomplex by the DNA-dependent Protein Kinase Enhances Its Histone Deacetylase Activity. J. Biol. Chem. 282: 9312-9322 [Abstract] [Full Text]  
  • Chen, Y., Schnetz, M. P., Irarrazabal, C. E., Shen, R.-F., Williams, C. K., Burg, M. B., Ferraris, J. D. (2007). Proteomic identification of proteins associated with the osmoregulatory transcription factor TonEBP/OREBP: functional effects of Hsp90 and PARP-1. Am. J. Physiol. Renal Physiol. 292: F981-F992 [Abstract] [Full Text]  
  • Yung, T. M. C., Sato, S., Satoh, M. S. (2004). Poly(ADP-ribosyl)ation as a DNA Damage-induced Post-translational Modification Regulating Poly(ADP-ribose) Polymerase-1-Topoisomerase I Interaction. J. Biol. Chem. 279: 39686-39696 [Abstract] [Full Text]  
  • Ko, L., Chin, W. W. (2003). Nuclear Receptor Coactivator Thyroid Hormone Receptor-binding Protein (TRBP) Interacts with and Stimulates Its Associated DNA-dependent Protein Kinase. J. Biol. Chem. 278: 11471-11479 [Abstract] [Full Text]  
  • Virag, L., Szabo, C. (2002). The Therapeutic Potential of Poly(ADP-Ribose) Polymerase Inhibitors. Pharmacol. Rev. 54: 375-429 [Abstract] [Full Text]  
  • Carty, S. M., Greenleaf, A. L. (2002). Hyperphosphorylated C-terminal Repeat Domain-associating Proteins in the Nuclear Proteome Link Transcription to DNA/Chromatin Modification and RNA Processing. Mol. Cell. Proteomics 1: 598-610 [Abstract] [Full Text]  
  • Soldatenkov, V. A., Chasovskikh, S., Potaman, V. N., Trofimova, I., Smulson, M. E., Dritschilo, A. (2002). Transcriptional Repression by Binding of Poly(ADP-ribose) Polymerase to Promoter Sequences. J. Biol. Chem. 277: 665-670 [Abstract] [Full Text]  
  • Hassa, P. O., Covic, M., Hasan, S., Imhof, R., Hottiger, M. O. (2001). The Enzymatic and DNA Binding Activity of PARP-1 Are Not Required for NF-kappa B Coactivator Function. J. Biol. Chem. 276: 45588-45597 [Abstract] [Full Text]  
  • Ishizuka, T., Satoh, T., Monden, T., Shibusawa, N., Hashida, T., Yamada, M., Mori, M. (2001). Human Immunodeficiency Virus Type 1 Tat Binding Protein-1 Is a Transcriptional Coactivator Specific for TR. Mol. Endocrinol. 15: 1329-1343 [Abstract] [Full Text]  
  • Storozhenko, S., Inze, D., Van Montagu, M., Kushnir, S. (2001). Arabidopsis coactivator ALY-like proteins, DIP1 and DIP2, interact physically with the DNA-binding domain of the Zn-finger poly(ADP-ribose) polymerase. J Exp Bot 52: 1375-1380 [Abstract] [Full Text]  
  • Li, H.-C., Liu, D., Waxman, D. J. (2001). Transcriptional Induction of Hepatic NADPH: Cytochrome P450 Oxidoreductase by Thyroid Hormone. Mol. Pharmacol. 59: 987-995 [Abstract] [Full Text]  
  • Cesarone, C. F., Scarabelli, L., Demori, I., Balocco, S., Fugassa, E. (2000). Poly(ADP-ribose) polymerase is affected early by thyroid state during liver regeneration in rats. Am. J. Physiol. Gastrointest. Liver Physiol. 279: G1219-G1225 [Abstract] [Full Text]  
  • Cervellera, M. N., Sala, A. (2000). Poly(ADP-ribose) Polymerase Is a B-MYB Coactivator. J. Biol. Chem. 275: 10692-10696 [Abstract] [Full Text]  
  • Nirodi, C., NagDas, S., Gygi, S. P., Olson, G., Aebersold, R., Richmond, A. (2001). A Role for Poly(ADP-ribose) Polymerase in the Transcriptional Regulation of the Melanoma Growth Stimulatory Activity (CXCL1) Gene Expression. J. Biol. Chem. 276: 9366-9374 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»