AR (androgen receptor) is a member of the nuclear receptor, it is not only mature men, but also plays an important role in the progress of prostate cancer. SMRT (silencingmediator for retinoid andthyroidhormonereceptor) is a nuclear receptor-assisted inhibitor, is currently a large number of research results indicate that SMRT, the activity of many nuclear receptors such as ER, PR, inhibited the balance of hormonal fluctuation plays an important role . However, the relationship between AR and SMRT how little research. The purpose of this study AR whether SMRT and its site of action.
Gal42DBD fusion protein analysis showed that the AR with a certain degree of transcriptional repression activity, the inhibitory activity of the region is the region of the AR molecule E. I found the the AR2N side A / B contains a strong transcriptional activation function, this activity can not be complete AR molecule the performance, G42AR, fusion protein inhibited the ability of the basal transcription activity and AR can inhibit factor SMRT interaction is consistent. Two-hybrid experiments in mammalian cells prompted SMRT phase and the ARA / B and E section. Body of experimental results, further in vitro GST precipitation assay confirmed, indicate that SMRT through SMRT2ID2 directly interact with AR. While SMRT2ID1 and AR affinity. ID1 and ID2 common LXXXIXXXI / L sequence-mediated SMRT or N2COR, and nuclear receptor combining. Interestingly, when LXXXIXXXI / L, secondary suppression mutation of the functional groups, SMRT2AR interaction was inhibited, suggesting that SMRT with AR binding mechanism may be similar to other nuclear receptors.
AR protein molecules combining two sites with SMRT, the exact mechanism remains to be clarified. Combination of the strongest and SMRT fragment is the carboxyl terminus of AR 501 2919 District This fragment contains the DNA binding domain (DBD) and ligand binding domain (LBD), the LBD can be alone with SMRT, while the DBD but not .Suggesting that the LBD is the SMRT-binding site, the presence of the DBD District will help to stabilize the LBD conformation in order to better integrate with SMRT. Or section DBD SMRT weak binding ability of this site may be synergistic combination of LBD and SMRT. Similarly, ARDBD the configuration of the stability of the A / area, making it the ability to bind with SMRT. Contrary to the reports of Smith et al, in the GST precipitation assay use cSMRT or SM2RT2ID2, ARA / B and SMRT can not, however, SMRT is very easy and ARLBD combination prompted the LBD is a the SMRT combination of good parts. Seems LBD and reported that the A / B binding site need to SMRT2ID2 area structural integrity of the LXXXIXXXI / L functional groups, suggesting that the the SMRT combination of mechanisms related to ARLBD or A / B area. ID1 and ID2 secondary inhibition of groups of gene sequences, AR molecules to identify the ID1 or ID2 nucleotide sequence of the mechanism is unclear.
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