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|Title:||GRIP1 mediates the interaction between the amino- and carboxyl-termini of the androgen receptor.|
|Citation:||Journal of Biological Chemistry, 2005; 386(1):69-74|
|Publisher:||Amer Soc Biochemistry Molecular Biology Inc|
|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|
|Appears in Collections:||Medicine publications|
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