This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Park, Y.-Y. Articles by Choi, H.-S. Search for Related Content PubMed PubMed Citation Articles by Park, Y.-Y. Articles by Choi, H.-S.

Differential Role of the Loop Region between Helices H6 and H7 within the Orphan Nuclear Receptors Small Heterodimer Partner and DAX-1

Hormone Research Center (Y.-Y.P., H.-J.K., J.-Y.K., M.-Y.K., K.-H.S., H.-S.C.), School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757; KOMED Institute for Life Science (K.-Y.Y.), Graduate School of Biotechnology, Korea University, Seoul 136-701; Laboratory of Endocrine Cell Biology (K.C.P., M.S.), Department of Internal Medicine, Chungnam National University School of Medicine, Daejon 301-721; and R&D Park (K.-H.K.), LG Life Sciences, Ltd., Daejeon 305-380, Republic of Korea

Address all correspondence and requests for reprints to: Hueung-Sik Choi, Ph.D., Hormone Research Center, Chonnam National University, Gwangju 500-757, Republic of Korea. E-mail: hsc{at}chonnam.chonnam.ac.kr.

The orphan nuclear receptors small heterodimer partner (SHP) and dosage-sensitive sex-reversal adrenal hypoplasia congenital (AHC) critical region on the X chromosome gene 1 (DAX-1) contain extra amino acids between helices H6 and H7 of LBD, and here we investigated a possible role of these additional amino acids. Transient transfection assay demonstrated that, in contrast to wild type, in mutant SHP 128–139 deletion of 12 extra amino acids in H6-H7 failed to repress the transactivity of orphan nuclear receptors such as estrogen receptor-related receptor-, hepatocyte nuclear factor 4, and constitutive androstane receptor. Interestingly, yeast two-hybrid and glutathione-S-transferase pull-down assays demonstrated that wild-type and SHP 128–139 have similar abilities to interact with estrogen receptor-related receptor-, hepatocyte nuclear factor 4, and constitutive androstane receptor. Unexpectedly, in wild-type DAX-1 and mutant DAX-1 338–362, deletion of 25 extra amino acids in H6-H7 had no significant difference in the interaction and repression of steroidogenic factor 1 transactivation. Mutant SHP that contains DAX-1 extra amino acids or polyalanine stretch in H6-H7 showed indistinguishable pattern of repression from wild-type SHP. Interestingly, the swapped SHP mutant with DAX-1 extra amino acids interacted with EID-1 (E1A-like inhibitor of differentiation 1), which is characterized as an SHP-interacting corepressor. However, interaction between SHP 128–139 and EID-1 was significantly diminished. Moreover, SHP-mediated repression of constitutive androstane receptor transactivation was significantly released by down-regulation of EID-1 expression with EID-1 small interfering RNA. The present study suggests that H6-H7 loop regions of SHP and DAX-1 play a different role in the repression of nuclear receptor transactivation.

NURSA Molecule Pages Link:

Nuclear Receptors:   DAX1  |  SHP  |  CAR  |  HNF4α  |  ERRγ  |  SF-1  |  LRH-1

Coregulators:   SRC-1

This article has been cited by other articles:

				I. P. Y. Lam, L. T. O. Lee, H.-S. Choi, G. Alpini, and B. K. C. Chow Bile acids inhibit duodenal secretin expression via orphan nuclear receptor small heterodimer partner (SHP) Am J Physiol Gastrointest Liver Physiol, July 1, 2009; 297(1): G90 - G97. [Abstract] [Full Text] [PDF]

				Y.-B. Xie, B. Nedumaran, and H.-S. Choi Molecular characterization of SMILE as a novel corepressor of nuclear receptors Nucleic Acids Res., May 8, 2009; (2009) gkp333v1. [Abstract] [Full Text] [PDF]

				E. P. Sablin, A. Woods, I. N. Krylova, P. Hwang, H. A. Ingraham, and R. J. Fletterick The structure of corepressor Dax-1 bound to its target nuclear receptor LRH-1 PNAS, November 25, 2008; 105(47): 18390 - 18395. [Abstract] [Full Text] [PDF]

				Y. D. Kim, K.-G. Park, Y.-S. Lee, Y.-Y. Park, D.-K. Kim, B. Nedumaran, W. G. Jang, W.-J. Cho, J. Ha, I.-K. Lee, et al. Metformin Inhibits Hepatic Gluconeogenesis Through AMP-Activated Protein Kinase-Dependent Regulation of the Orphan Nuclear Receptor SHP Diabetes, February 1, 2008; 57(2): 306 - 314. [Abstract] [Full Text] [PDF]

				J. H. Suh, J. Huang, Y.-Y. Park, H.-A Seong, D. Kim, M. Shong, H. Ha, I.-K. Lee, K. Lee, L. Wang, et al. Orphan Nuclear Receptor Small Heterodimer Partner Inhibits Transforming Growth Factor-beta Signaling by Repressing SMAD3 Transactivation J. Biol. Chem., December 22, 2006; 281(51): 39169 - 39178. [Abstract] [Full Text] [PDF]

				K.-H. Song, Y.-Y. Park, H. J. Kee, C. Y. Hong, Y.-S. Lee, S.-W. Ahn, H.-J. Kim, K. Lee, H. Kook, I.-K. Lee, et al. Orphan Nuclear Receptor Nur77 Induces Zinc Finger Protein GIOT-1 Gene Expression, and GIOT-1 Acts as a Novel Corepressor of Orphan Nuclear Receptor SF-1 via Recruitment of HDAC2 J. Biol. Chem., June 9, 2006; 281(23): 15605 - 15614. [Abstract] [Full Text] [PDF]

				Y.-Y. Park, S.-W. Ahn, H.-J. Kim, J.-M. Kim, I.-K. Lee, H. Kang, and H.-S. Choi An autoregulatory loop controlling orphan nuclear receptor DAX-1 gene expression by orphan nuclear receptor ERR{gamma} Nucleic Acids Res., November 28, 2005; 33(21): 6756 - 6768. [Abstract] [Full Text] [PDF]

				M. G. Yeo, Y.-G. Yoo, H.-S. Choi, Y. K. Pak, and M.-O. Lee Negative Cross-Talk between Nur77 and Small Heterodimer Partner and Its Role in Apoptotic Cell Death of Hepatoma Cells Mol. Endocrinol., April 1, 2005; 19(4): 950 - 963. [Abstract] [Full Text] [PDF]

				J.-Y. Kim, H.-J. Kim, K. T. Kim, Y.-Y. Park, H.-A Seong, K. C. Park, I.-K. Lee, H. Ha, M. Shong, S. C. Park, et al. Orphan Nuclear Receptor Small Heterodimer Partner Represses Hepatocyte Nuclear Factor 3/Foxa Transactivation via Inhibition of Its DNA Binding Mol. Endocrinol., December 1, 2004; 18(12): 2880 - 2894. [Abstract] [Full Text] [PDF]