Document Detail


Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminus.
MedLine Citation:
PMID:  11854421     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The androgen receptor (AR) is a ligand-regulated transcription factor that stimulates cell growth and differentiation in androgen-responsive tissues. The AR N terminus contains two activation functions (AF-1a and AF-1b) that are necessary for maximal transcriptional enhancement by the receptor; however, the mechanisms and components regulating AR transcriptional activation are not fully understood. We sought to identify novel factors that interact with the AR N terminus from an androgen-stimulated human prostate cancer cell library using a yeast two-hybrid approach designed to identify proteins that interact with transcriptional activation domains. A 157-amino acid protein termed ART-27 was cloned and shown to interact predominantly with the AR(153-336), containing AF-1a and a part of AF-1b, localize to the nucleus and increase the transcriptional activity of AR when overexpressed in cultured mammalian cells. ART-27 also enhanced the transcriptional activation by AR(153-336) fused to the LexA DNA-binding domain but not other AR N-terminal subdomains, suggesting that ART-27 exerts its effect via an interaction with a defined region of the AR N terminus. ART-27 interacts with AR in nuclear extracts from LNCaP cells in a ligand-independent manner. Interestingly, velocity gradient sedimentation of HeLa nuclear extracts suggests that native ART-27 is part of a multiprotein complex. ART-27 is expressed in a variety of human tissues, including sites of androgen action such as prostate and skeletal muscle, and is conserved throughout evolution. Thus, ART-27 is a novel cofactor that interacts with the AR N terminus and plays a role in facilitating receptor-induced transcriptional activation.
Authors:
Steven M Markus; Samir S Taneja; Susan K Logan; Wenhui Li; Susan Ha; Adam B Hittelman; Inez Rogatsky; Michael J Garabedian
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular biology of the cell     Volume:  13     ISSN:  1059-1524     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-02-20     Completed Date:  2002-06-20     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  670-82     Citation Subset:  IM    
Affiliation:
Department of Microbiology, The Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Gene Expression Regulation
Humans
Molecular Sequence Data
Neoplasm Proteins
Receptors, Androgen / genetics,  metabolism*
Trans-Activators / genetics*,  metabolism
Tumor Cells, Cultured
Two-Hybrid System Techniques
Grant Support
ID/Acronym/Agency:
2T32 GM-07308/GM/NIGMS NIH HHS; 5T32 AI-07180/AI/NIAID NIH HHS; K08 DK-02577/DK/NIDDK NIH HHS; P30 CA-16087/CA/NCI NIH HHS; R01 DK-58024/DK/NIDDK NIH HHS; T32 DK-07775/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Neoplasm Proteins; 0/Receptors, Androgen; 0/Trans-Activators; 0/UXT protein, human
Comments/Corrections

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