Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/37055
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Type: Journal article
Title: GRIP1 mediates the interaction between the amino- and carboxyl-termini of the androgen receptor.
Author: Shen, H.
Buchanan, G.
Butler, L.
Prescott, J.
Henderson, M.
Tilley, W.
Coetzee, G.
Citation: Journal of Biological Chemistry, 2005; 386(1):69-74
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Issue Date: 2005
ISSN: 0021-9258
1437-4315
Statement of
Responsibility: 
Howard C. Shen, Grant Buchanan, Lisa M. Butler, Jennifer Prescott, Michael Henderson, Wayne D. Tilley and Gerhard A. Coetzee
Abstract: The androgen receptor (AR) mediates transactivation of target genes by acting as a dimer in which its aminoterminal domain (AR-NTD) interacts with its carboxyl-terminal, ligand-binding domain (AR-LBD) (N/C interaction). Here we assessed if and how AR N/C interaction relates to AR transactivation activity and how the p160 coactivator GRIP1 participates in both processes. The concentration of dihydrotestosterone needed for half-maximal N/C interaction was approximately 10-fold higher than for half-maximal transactivation, indicating a disparity between the two processes. Although a mutation of an LXXLL-like motif, 23FQNLF27™23FQNAA27, in the AR-NTD abolished AR N/C interaction, it could be restored by the co-expression of the coactivator GRIP1. Co-expression of mutated forms of GRIP1, possessing alterations known to abolish either of the two AR interaction domains, could not restore AR N/C interaction, suggesting that wild-type GRIP1 normally bridges the two AR domains. Although AR transactivation activity can proceed without AR N/C interaction, we propose that part of the GRIP1 coactivation activity resides in its ability to bind both AR-NTD and -LBD, to stabilize the N/C complex and allow for secondary cofactors to be recruited more efficiently. Our results also indicate that AR N/C interaction enhances but is not necessary for AR transactivation activity.
Keywords: androgen receptor; coactivator; dimerization; domain interactions; transactivation; transcription
Description: © 2005 by Walter de Gruyter
RMID: 0020065961
DOI: 10.1515/BC.2005.009
Appears in Collections:Medicine publications

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