HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Volakakis, N. Articles by Benoit, G. Search for Related Content PubMed PubMed Citation Articles by Volakakis, N. Articles by Benoit, G.

Ludwig Institute for Cancer Research, Stockholm Branch, Box 240, S-171 77 Stockholm, Sweden
¹ Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden

(Requests for offprints should be addressed to T Perlmann; Email: thomas.perlmann{at}licr.ki.se)

G Benoit is now at CNRS UMR 5161, Laboratoire de Biologie Moléculaire de la Cellule, IFR128 BioSciences Lyon-Gerland, École Normale Supérieure de Lyon, 46 Allée d’Italie, 69364 Lyon Cedex 07, France

The recently solved crystal structure of the orphan nuclear receptor (NR) Nurr1 ligand-binding domain (LBD) showed that Nurr1 lacks a cavity for ligand binding and a canonical NR co-activator-binding site. Computer modeling of the Nurr1 LBD structure identified a hydrophobic region on the surface of the Nurr1 LBD that was positioned on the opposite side from the classical co-activator-binding site. Site-directed mutagenesis demonstrated that this region is critical for the activity of the Nurr1 LBD. Most mutations introduced in this region reduced or abolished transcriptional activity of the Nurr1 LBD, but mutation at lysine (K577) resulted in a drastically increased activity. Moreover, the activity of the Nurr1 LBD was shown to correlate with a propensity for proteasome-dependent degradation revealing a close association between activity and Nurr1 protein turnover. These data provide novel insights into the mechanisms of transcription via the Nurr1 LBD and identify an alternative co-activator-binding surface that is unique to the NR4A family of NRs.

This article has been cited by other articles:

				F. M. J. Jacobs, S. van Erp, A. J. A. van der Linden, L. von Oerthel, J. P. H. Burbach, and M. P. Smidt Pitx3 potentiates Nurr1 in dopamine neuron terminal differentiation through release of SMRT-mediated repression Development, February 15, 2009; 136(4): 531 - 540. [Abstract] [Full Text] [PDF]

				H. Kitagawa, W. J. Ray, H. Glantschnig, P. V. Nantermet, Y. Yu, C.-T. Leu, S.-i. Harada, S. Kato, and L. P. Freedman A Regulatory Circuit Mediating Convergence between Nurr1 Transcriptional Regulation and Wnt Signaling Mol. Cell. Biol., November 1, 2007; 27(21): 7486 - 7496. [Abstract] [Full Text] [PDF]

				G. Benoit, A. Cooney, V. Giguere, H. Ingraham, M. Lazar, G. Muscat, T. Perlmann, J.-P. Renaud, J. Schwabe, F. Sladek, et al. International Union of Pharmacology. LXVI. Orphan Nuclear Receptors Pharmacol. Rev., December 1, 2006; 58(4): 798 - 836. [Abstract] [Full Text] [PDF]