Document Detail

Analysis of ligand-dependent recruitment of coactivator peptides to RXRbeta in a time-resolved fluorescence resonance energy transfer assay.
MedLine Citation:
PMID:  17184907     Owner:  NLM     Status:  MEDLINE    
Because RXR plays a significant role in nuclear receptor signaling as a common heterodimeric partner for TR, PPAR, RAR, VDR, LXR and others, the ability of RXRbeta ligand binding domain (LBD) to interact with coregulator peptides bearing LXXLL or other interaction motifs was investigated using time-resolved fluorescence resonance energy transfer (TR-FRET). The random phage display peptide D22 and peptides derived from PGC1alpha, SRC1-4, SRC2-3, PRIP/RAP250 and RIP140 yielded the highest TR-FRET signal with RXRbeta LBD in the presence of saturating 9-cis retinoic acid (9-cisRA). Several peptides including D22, PGC1alpha, SRC3-2, PRIP/RAP250 and SRC1-4 also formed a complex with RXRbeta LBD in the presence of all-trans retinoic acid (at-RA) and the fatty acids, phytanic acid (PA) and docosahexaenoic acid (DHA). Determination of the dose dependency (EC50) of these compounds to recruit D22 to RXRbeta LBD indicated that the rank order potency was 9-cisRA>PA>at-RA>DHA. The ligands 9-cisRA and at-RA yielded an overall higher fold-change in D22 recruitment to RXRbeta LBD suggesting that more RXRbeta LBD-D22 complex was formed in the presence of these ligands under the assay conditions tested. The statistical parameter Z' factor for 9-cisRA-induced recruitment of D22 to RXRbeta LBD was 0.6 after 2h incubation, indicating a robust methodology that could be applied to high throughput screening. These results demonstrate that RXRbeta occupied with the fatty acid ligands, DHA and PA, can recruit coactivator peptides in a ligand-dependent manner.
Deborah K Stafslien; Kevin L Vedvik; Therese De Rosier; Mary Szatkowski Ozers
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Publication Detail:
Type:  Journal Article     Date:  2006-12-20
Journal Detail:
Title:  Molecular and cellular endocrinology     Volume:  264     ISSN:  0303-7207     ISO Abbreviation:  Mol. Cell. Endocrinol.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-22     Completed Date:  2007-03-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7500844     Medline TA:  Mol Cell Endocrinol     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  82-9     Citation Subset:  IM    
Invitrogen Discovery Sciences, Madison, Wisconsin 53719, USA.
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MeSH Terms
Adaptor Proteins, Signal Transducing / chemistry*,  metabolism
Amino Acid Motifs
Fluorescence Resonance Energy Transfer*
Peptides / chemistry*
Protein Binding / physiology
Protein Structure, Tertiary / physiology
Retinoid X Receptor beta / chemistry*,  metabolism
Signal Transduction / drug effects,  physiology
Tretinoin / chemistry,  pharmacology
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Ligands; 0/Peptides; 0/Retinoid X Receptor beta; 302-79-4/Tretinoin

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