Tip60 is a co-activator specific for class I nuclear hormone receptors

被引:78
作者
Gaughan, L [1 ]
Brady, ME [1 ]
Cook, S [1 ]
Neal, DE [1 ]
Robson, CN [1 ]
机构
[1] Univ Newcastle Upon Tyne, Sch Med, Prostate Res Grp, Sch Surg Sci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
关键词
D O I
10.1074/jbc.M103710200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The nuclear hormone receptor superfamily is composed of a group of hormone-dependent transcription factors that play prominent roles in homeostatic events in vertebrates. A prerequisite for steroid hormone receptor activity is the binding of co-activator molecules to the activation function-2 domain of the receptor. The LXXLL motif/nuclear receptor box, contained within a number of co-activator molecules, mediates the interaction with nuclear hormone receptors. Tip60 (Tat-interactive protein 60 kDa), previously shown to bind to and enhance androgen receptor (AR)-mediated transactivation, contains a single nuclear receptor box at its extreme C terminus. We demonstrate that unlike members of the p160 co-activator family that interact predominantly with the N terminus of the AR in an LXXLL motif-independent manner, the LXXLL motif of Tip60 is required and is sufficient for AR interaction. Furthermore, by using the mammalian two-hybrid system and transient transfection experiments, we show that Tip60 preferentially interacts with and up-regulates class I nuclear receptors, suggesting that Tip60 is a steroid hormone receptor-specific co-activator. We conclude that Tip60 may specifically regulate a subset of nuclear hormone receptors, giving an indication to how regulated nuclear receptor activation can be achieved.
引用
收藏
页码:46841 / 46848
页数:8
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