MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
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 Suzuki, T.
Right arrow Articles by Umesono, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Suzuki, T.
Right arrow Articles by Umesono, K.
Molecular and Cellular Biology, January 2003, p. 238-249, Vol. 23, No. 1
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.1.238-249.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

LXXLL-Related Motifs in Dax-1 Have Target Specificity for the Orphan Nuclear Receptors Ad4BP/SF-1 and LRH-1

Taiga Suzuki,1,2 Megumi Kasahara,3 Hidefumi Yoshioka,3 Ken-ichirou Morohashi,1,4* and Kazuhiko Umesono2,5

Department of Developmental Biology, National Institute for Basic Biology, Okazaki 444-8585,1 Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507,2 Department of Natural Sciences, Hyogo University of Teacher Education, Hyogo 673-1494,3 Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Kawaguchi 332-0012,4 Graduate School for Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan5

Received 5 April 2002/ Returned for modification 25 June 2002/ Accepted 24 September 2002

The orphan receptor Ad4BP/SF-1 (NR5A1) is a constitutive activator, and its activity is repressed by another orphan receptor, Dax-1 (NR0B1). In the present study, we investigated the molecular mechanisms underlying this repression by Dax-1. Yeast two-hybrid and transient-transfection assays confirmed the necessity of three LXXLL-related motifs in Dax-1 for interaction with and repression of Ad4BP/SF-1. In vitro pull-down experiments confirmed that Dax-1 interacts with Ad4BP/SF-1 and also with LRH-1 (NR5A2). The target specificity of the LXXLL-related motifs was indicated by the observations that Ad4BP/SF-1, ER{alpha} (NR3A1), LRH-1, ERR2 (NR3B2), and fly FTZ-F1 (NR5A3) interacted through their ligand binding domains with all the LXXLL-related motifs in Dax-1 whereas HNF4 (NR2A1) and ROR{alpha} (NR1F1) did not. Transcriptional activities of the receptors whose DNA binding domains (DBDs) were replaced by the GAL4 DBD were repressed by Dax-1 to various levels, which correlated with the strength of interaction. Amino acid substitutions revealed that Ad4BP/SF-1 and LRH-1 preferentially interact with L(+1)XXLL-related motifs containing serine, tyrosine, serine, and threonine at positions -2, +2, +3, and +6, respectively. Taken together, our results indicate that the specificities of LXXLL-related motifs in Dax-1 based on their amino acid sequences play an important role in regulation of orphan receptors.

* Corresponding author. Mailing address: Department of Developmental Biology, National Institute for Basic Biology, Myodaiji-cho, Okazaki 444-8585, Japan. Phone: 81-564-55-7560. Fax: 81-564-55-7561. E-mail: moro{at}nibb.ac.jp.

Molecular and Cellular Biology, January 2003, p. 238-249, Vol. 23, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.1.238-249.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2003 by the American Society for Microbiology. All rights reserved.