c-Jun potentiates the functional interaction between the amino and carboxyl termini of the androgen receptor
c-Jun potentiates the functional interaction between the amino and carboxyl termini of the androgen receptor
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DOI：
10.1074/jbc.m107346200
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发表时间：
2001-11-30
影响因子：
4.8
通讯作者：
Shemshedini, L
中科院分区：
文献类型：
--
作者：
Bubulya, A;Chen, SY;Shemshedini, L
人雄激素受体（hAR）的交互激活功能受几个辅助因素的调节，这些辅助因素可能是正的，也可能是负的。一个先前被证明介导hAR转录激活的因子是原癌蛋白c-Jun。正效应是主要效应，内源性和外源性c-Jun都能发挥作用，需要c-Jun的多个区域发挥作用。然而，c-Jun发挥其增强作用的确切机制尚不清楚。在这项研究中，我们使用哺乳动物双杂交系统来询问c-Jun是否影响hAR的配体依赖性氨基-羧基端（N-to-C）相互作用，这被认为是该受体同二聚化的原因。我们的研究结果表明，e-Jun在体外增强了hAR N-to-C末端相互作用和DNA结合。我们还测试了一组c-Jun和c-Fos突变体对N-to-C相互作用的活性，数据表明这些突变体的活性与它们对hAR交互作用的活性相似。hAR激活功能-2 （AF-2）的突变取消了n- c相互作用，DNA结合和反活化，并且这些活性不会被外源c-Jun挽救。有趣的是，p160共激活子TIF2可以刺激hAR n - c相互作用，这一发现与对hAR交互激活的影响一致。这些数据有力地表明，hAR n - c相互作用是c-Jun作用的目标，而这种作用需要功能性受体AF-2。
The transactivation functions of the human androgen receptor (hAR) are regulated by several accessory factors that can be either positive or negative. One factor that has been previously shown to mediate hAR transactivation is the proto-oncoprotein c-Jun. The positive effect is a primary one, can be exerted by both endogenous and exogenous c-Jun, and requires multiple regions of c-Jun. However, the exact mechanism by which c-Jun exerts its enhancing function is unknown. In this study, we have used a mammalian two-hybrid system to ask if c-Jun influences the ligand-dependent amino- to carboxyl-terminal (N-to-C) interaction of hAR, which is thought to be responsible for the homodimerization of this receptor. Our results show that e-Jun enhances both hAR N-to-C terminal interaction and DNA binding in vitro. We have also tested a panel of c-Jun and c-Fos mutants for their activities on the N-to-C interaction, and the data demonstrate that the activities of these mutants parallel their activities on hAR transactivation. A mutation in the hAR activation function-2 (AF-2) abrogates N-to-C interaction, DNA binding, and transactivation, and these activities are not rescued by exogenous c-Jun. Interestingly, the p160 coactivator TIF2 can stimulate hAR N-to-C interaction, a finding consistent with the effect on hAR transactivation. These data strongly suggest that the hAR N-to-C interaction is the target of c-Jun action, and this activity requires a functional receptor AF-2.