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Differential role of the loop region between helices H6 and H7 within the orphan nuclear receptors small heterodimer partner and DAX-1

 Yun-Yong Park  ;  Han-Jong Kim  ;  Hueng-Sik Choi  ;  Kyoung-Hee Kim  ;  Minho Shong  ;  Kang-Yeol Yu  ;  Ki Cheol Park  ;  Kwang-Hoon Song  ;  Mi-Young Kim  ;  Joon-Young Kim 
 MOLECULAR ENDOCRINOLOGY , Vol.18(5) : 1082-1095, 2004 
Journal Title
Issue Date
Amino Acid Sequence ; Animals ; COS Cells ; Cercopithecus aethiops ; DAX-1 Orphan Nuclear Receptor ; DNA-Binding Proteins/genetics* ; DNA-Binding Proteins/metabolism ; Gene Expression Regulation ; Humans ; Models, Molecular* ; Molecular Sequence Data ; Mutation/genetics ; Receptors, Cytoplasmic and Nuclear/genetics* ; Receptors, Cytoplasmic and Nuclear/metabolism ; Receptors, Retinoic Acid/genetics* ; Receptors, Retinoic Acid/metabolism ; Repressor Proteins/genetics* ; Repressor Proteins/metabolism ; Steroidogenic Factor 1 ; Trans-Activators/genetics ; Transcription, Genetic ; Tumor Cells, Cultured ; X Chromosome/genetics* ; X Chromosome/metabolism
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 Delta128-139 deletion of 12 extra amino acids in H6-H7 failed to repress the transactivity of orphan nuclear receptors such as estrogen receptor-related receptor-gamma, hepatocyte nuclear factor 4alpha, and constitutive androstane receptor. Interestingly, yeast two-hybrid and glutathione-S-transferase pull-down assays demonstrated that wild-type and SHP Delta128-139 have similar abilities to interact with estrogen receptor-related receptor-gamma, hepatocyte nuclear factor 4alpha, and constitutive androstane receptor. Unexpectedly, in wild-type DAX-1 and mutant DAX-1 Delta338-362, 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 Delta128-139 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
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Mi Young(김미영)
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