Journal Mobile Options
Table of Contents
Vol. 23, No. 1, 2001
Issue release date: January–February 2001
Dev Neurosci 2001;23:17–24
(DOI:10.1159/000048692)

The Orphan Nuclear Receptor NOR-1 Interacts with the Homeobox Containing Protein Six31

Ohkura N. · Ohkubo T. · Maruyama K. · Tsukada T. · Yamaguchi K.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Neuron-derived orphan receptor 1 (NOR-1) is a member of the NGFI-B subfamily within the nuclear receptor superfamily. In order to identify cofactors that associate with NOR-1 in the fetal forebrain, we tested a yeast two-hybrid system with the NOR-1 cDNA fragment lacking a transactivating domain as a bait. By screening of the rat fetal brain embryonic day 17 library, a rat homologue of Six3 was identified as an associated protein. We demonstrated that NOR-1 interacted with Six3 in yeast and in vitro, and the association was required for the DNA binding and AF2 domains of NOR-1. Regarding the other members of the family (NGFI-B and RNR-1), association with Six3 was not observed in yeast. In addition, cotransfection experiments with Six3 and NOR-1 indicated that Six3 had a negative activity against the transactivation by NOR-1 through the NBRE response element in a dose- dependent manner. The overlap in expression of NOR-1 and Six3 was mainly detected in the rat fetal forebrain on embryonic day 18. Thereafter, the expression of both genes diminished rapidly. These results suggest that a dimer consisting of a homeobox containing protein Six3 and transcriptional factor NOR-1 might regulate gene expression during the late stage of the fetal forebrain development. This study provides, after the association of Ftz and Ftz-F1 in Drosophila, another example of a dimer formation of a homeobox protein and an orphan nuclear receptor.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Ohkura N, Hijikuro M, Yamamoto A, Miki K: Molecular cloning of a novel thyroid/steroid receptor superfamily gene from cultured rat neuronal cells. Biochem Biophys Res Commun 1994;205:1959–1965.
  2. Milbrandt J: Nerve growth factor induces a gene homologous to the glucocorticoid receptor gene. Neuron 1988;1:183–188.

    External Resources

  3. Hazel TG, Nathans D, Lau LF: A gene inducible by serum growth factors encodes a member of the steroid and thyroid hormone receptor superfamily. Proc Natl Acad Sci USA 1988;85:8444–8448.
  4. Chang C, Kokontis J, Liao SS, Chang Y: Isolation and characterization of human TR3 receptor: A member of steroid receptor superfamily. J Steroid Biochem 1989;34:391–395.
  5. Scearce LM, Laz TM, Hazel TG, Lau LF, Taub R: RNR-1, a nuclear receptor in the NGFI-B/Nur77 family that is rapidly induced in regenerating liver. J Biol Chem 1993;268:8855–8861.

    External Resources

  6. Law SW, Conneely OM, DeMayo FJ, O’Malley BW: Identification of a new brain-specific transcription factor, NURR1. Mol Endocrinol 1992;6:2129–2135.
  7. Clark J, Benjamin H, Gill S, Sidhar S, Goodwin G, Crew J, Gusterson BA, Shipley J, Cooper CS: Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor gene superfamily, in a human myxoid chondrosarcoma. Oncogene 1996;12:229–235.
  8. Labelle Y, Zucman J, Stenman G, Kindblom L-G, Knight J, Turc-Carel C, Dockhorn-Dworniczak B, Mandahl N, Desmaze C, Peter M, Aurias A, Delattre O, Thomas G: Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation. Hum Mol Genet 1995;4:2219–2226.
  9. Liu Z-G, Smith SW, McLaughlin KA, Schwartz LM, Osborne BA: Apoptotic signals delivered through the T-cell receptor of a T-cell hybrid require the immediate-early gene nur77. Nature 1994;367:281–284.
  10. Woronicz JD, Calnan B, Ngo V, Winoto A: Requirement for the orphan steroid receptor Nur77 in apoptosis of T-cell hybridomas. Nature 1994;367:277–281.
  11. Katagiri Y, Hirata Y, Milbrandt J, Guroff G: Differential regulation of the transcriptional activity of the orphan nuclear receptor NGFI-B by membrane depolarization and nerve growth factor. J Biol Chem 1997;272:31278–31284.
  12. Bondy GP: Phorbol ester, forskolin, and serum induction of a human colon nuclear hormone receptor gene related to the NUR 77/NGFI-B genes. Cell Growth Differ 1991;2:203–208.
  13. Bandoh S, Tsukada T, Maruyama K, Ohkura N, Yamaguchi K: Gene expression of NOR-1, a neuron-derived orphan receptor, is inducible in neuronal and other cell lineages in culture. Mol Cell Endocrinol 1995;115:227–230.
  14. Zetterström RH, Solomin L, Jansson L, Hoffer BJ, Olson L, Perlmann T: Dopamine neuron agenesis in Nurr1-deficient mice. Science 1997;276:248–250.
  15. Zetterström RH, Solomin L, Mitsiadis T, Olson L, Perlmann T: Retinoid X receptor heterodimerization and developmental expression distinguish the orphan nuclear receptors NGFI-B, Nurr1, and Nor1. Mol Endocrinol 1996;10:1656–1666.

    External Resources

  16. Maruyama K, Tsukada T, Bandoh S, Sasaki K, Ohkura N, Yamaguchi K: Expression of the putative transcription factor NOR-1 in the nervous, the endocrine and the immune systems and the developing brain of the rat. Neuroendocrinology 1997;65:2–8.

    External Resources

  17. Ohkura N, Hijikuro M, Miki K: Antisense oligonucleotide to NOR-1, a novel orphan nuclear receptor, induces migration and neurite extension of cultured forebrain cells. Brain Res Mol Brain Res 1996;35:309–313.
  18. Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanata-phenol-chloroform extraction. Anal Biochem 1987;162:156–159.
  19. Laborda J: 36B4 cDNA used as an estradiol-independent mRNA control is the cDNA for human acidic ribosomal phosphoprotein PO. Nucleic Acids Res 1991;19:3998.
  20. Bandoh S, Tsukada T, Maruyama K, Ohkura N, Yamaguchi K: Differential expression of NGFI-B and RNR-1 genes in various tissues and developing brain of the rat: Comparative study by quantitative reverse transcription-polymerase chain reaction. J Neuroendocrinol 1997;9:3–8.
  21. Maruyama K, Tsukada T, Bandoh S, Sasaki K, Ohkura N, Yamaguchi K: Expression of NOR-1 and its closely related members of the steroid/thyroid hormone receptor superfamily in human neuroblastoma cell lines. Cancer Lett 1995;96:117–122.

    External Resources

  22. Ohkura N, Ito M, Tsukada T, Sasaki K, Yamaguchi K, Miki K: Structure, mapping and expression of a human NOR-1 gene, the third member of the Nur77/NGFI-B family. Biochem Biophys Acta 1996;1308:205–214.
  23. Schwartz JA, Brooks SC: Changes in the structure of the ligand or substitutions to AF2 residues in the estrogen receptor make independent contributions to coactivator sensitivity by SRC-1. J Steroid Biochem Mol Biol 1998;67:223–232.

    External Resources

  24. Wilson TE, Fahrner TJ, Johnston M, Milbrandt J: Identification of the DNA binding site for NGFI-B by genetic selection in yeast. Science 1991;252:1296–1300.

    External Resources

  25. Guichet A, Copeland JWR, Erdélyi M, Hlousek D, Závorszky P, Ho J, Brown S, Percival-Smith A, Kraus HM, Ephrussi A: The nuclear receptor homologue Ftz-F1 and the homeodomain protein Ftz are mutually dependent cofactors. Nature 1997;385:548–552.

    External Resources

  26. Yu Y, Li W, Su K, Yussa M, Han W, Perrimon N, Pick L: The nuclear hormone receptor Ftz-F1 is a cofactor for the Drosophila homeodomain protein Ftz. Nature 1997;385:552–555.
  27. Enmark E, Gustafsson J: Orphan nuclear receptors – the first eight years. Mol Endocrinol 1996;10:1293–1307.
  28. Oliver G, Mailhos A, Wehr R, Copeland NG, Jenkins NA, Griss P: Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. Development 1995;121:4045–4055.
  29. Cheyette BNR, Green PJ, Martin K, Garren H, Hartenstein V, Zipursky SL: The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system. Neuron 1994;12:977–996.
  30. Kobayashi M, Toyama T, Takeda H, Dawid IB, Kawakami K: Overexpression of the forebrain-specific homeobox gene six3 induces rostral forebrain enlargement in zebrafish. Development 1998;125:2973–2982.
  31. Wallis DE, Roessler E, Hehr U, Nanni L, Wiltshire T, Richieri-Costa A, Gillessen-Kaesbach G, Zackai EH, Rommens J, Muenke M: Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly. Nat Genet 1999;22:196–198.
  32. Hazbun TR, Stahura FL, Mossing MC: Site-specific recognition by an isolated DNA-binding domain of the sine oculis protein. Biochemistry 1997;36:3680–3686.

    External Resources



Pay-per-View Options
Direct payment This item at the regular price: USD 9.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 8.00