Document Detail


SMILE, a new orphan nuclear receptor SHP-interacting protein, regulates SHP-repressed estrogen receptor transactivation.
MedLine Citation:
PMID:  18657049     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
SHP (small heterodimer partner) is a well-known NR (nuclear receptor) co-regulator. In the present study, we have identified a new SHP-interacting protein, termed SMILE (SHP-interacting leucine zipper protein), which was previously designated as ZF (Zhangfei) via a yeast two-hybrid system. We have determined that the SMILE gene generates two isoforms [SMILE-L (long isoform of SMILE) and SMILE-S (short isoform of SMILE)]. Mutational analysis has demonstrated that the SMILE isoforms arise from the alternative usage of initiation codons. We have confirmed the in vivo interaction and co-localization of the SMILE isoforms and SHP. Domain-mapping analysis indicates that the entire N-terminus of SHP and the middle region of SMILE-L are involved in this interaction. Interestingly, the SMILE isoforms counteract the SHP repressive effect on the transactivation of ERs (estrogen receptors) in HEK-293T cells (human embryonic kidney cells expressing the large T-antigen of simian virus 40), but enhance the SHP-repressive effect in MCF-7, T47D and MDA-MB-435 cells. Knockdown of SMILE gene expression using siRNA (small interfering RNA) in MCF-7 cells increases ER-mediated transcriptional activity. Moreover, adenovirus-mediated overexpression of SMILE and SHP down-regulates estrogen-induced mRNA expression of the critical cell-cycle regulator E2F1. Collectively, these results indicate that SMILE isoforms regulate the inhibition of ER transactivation by SHP in a cell-type-specific manner and act as a novel transcriptional co-regulator in ER signalling.
Authors:
Yuan-Bin Xie; Ok-Hee Lee; Balachandar Nedumaran; Hyun-A Seong; Kyeong-Min Lee; Hyunjung Ha; In-Kyu Lee; Yungdae Yun; Hueng-Sik Choi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  416     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-25     Completed Date:  2009-01-30     Revised Date:  2009-04-16    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  463-73     Citation Subset:  IM    
Affiliation:
Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Basic-Leucine Zipper Transcription Factors / genetics,  metabolism*
Cell Line
E2F1 Transcription Factor / genetics,  metabolism
Humans
Leucine Zippers
Mice
Protein Isoforms / genetics,  metabolism*
RNA, Small Interfering / genetics,  metabolism
Receptors, Cytoplasmic and Nuclear / genetics,  metabolism*
Receptors, Estrogen / genetics,  metabolism*
Tissue Distribution
Transcription, Genetic
Transcriptional Activation*
Two-Hybrid System Techniques
Chemical
Reg. No./Substance:
0/Basic-Leucine Zipper Transcription Factors; 0/CREBZF protein, human; 0/E2F1 Transcription Factor; 0/E2F1 protein, human; 0/Protein Isoforms; 0/RNA, Small Interfering; 0/Receptors, Cytoplasmic and Nuclear; 0/Receptors, Estrogen; 0/nuclear receptor subfamily 0, group B, member 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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