Abstract
The androgen receptor (AR) mediates transactivation of target genes by acting as a dimer in which its amino-terminal 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.
Original language | English |
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Pages (from-to) | 69-74 |
Number of pages | 6 |
Journal | Biological Chemistry |
Volume | 386 |
Issue number | 1 |
DOIs | |
Publication status | Published or Issued - Jan 2005 |
Keywords
- Androgen receptor
- Coactivator
- Dimerization
- Domain interactions
- Transactivation
- Transcription
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Clinical Biochemistry