| SMILE, a new orphan nuclear receptor SHP-interacting protein, regulates SHP-repressed estrogen receptor transactivation. | |
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MedLine Citation:
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PMID: 18657049 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Biochemical journal Volume: 416 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-11-25 Completed Date: 2009-01-30 Revised Date: 2009-04-16 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
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Languages: eng Pagination: 463-73 Citation Subset: IM |
Affiliation:
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Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Republic of Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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 |
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