The LIM domain protein nTRIP6 recruits the mediator complex to AP-1-regulated promoters.
The LIM domain protein nTRIP6 recruits the mediator complex to AP-1-regulated promoters.
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DOI：
10.1371/journal.pone.0097549
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kassel O
中科院分区：
文献类型：
--
作者：
Diefenbacher ME;Reich D;Dahley O;Kemler D;Litfin M;Herrlich P;Kassel O
几种LIM结构域蛋白调节转录。它们被认为是通过其LIM蛋白-蛋白相互作用结构域作为衔接子来募集转录辅助调节因子。一个有趣的例子是nTRIP 6，粘着斑蛋白TRIP 6的核同种型。nTRIP 6与AP-1相互作用并增强其转录活性。nTRIP 6通过介导糖皮质激素受体（GR）与启动子结合的AP-1的束缚，对于AP-1的反式阻遏也是必需的。在这里，我们报告nTRIP 6发挥这些作用的分子机制。nTRIP 6的LIM结构域和前LIM区域对于其AP-1的共激活剂功能是必需的。前LIM区域内的离散结构域介导nTRIP 6在启动子处的二聚化，这使得能够募集介体复合物亚基THRAP 3和Med 1。通过GR和THRAP 3之间竞争与nTRIP 6的LIM结构域的相互作用，这种募集被GR阻断。因此，nTRIP 6通过协调介体复合物向AP-1调节的启动子的募集来正向和负向调节转录。
Several LIM domain proteins regulate transcription. They are thought to act through their LIM protein-protein interaction domains as adaptors for the recruitment of transcriptional co-regulators. An intriguing example is nTRIP6, the nuclear isoform of the focal adhesion protein TRIP6. nTRIP6 interacts with AP-1 and enhances its transcriptional activity. nTRIP6 is also essential for the transrepression of AP-1 by the glucocorticoid receptor (GR), by mediating GR tethering to promoter-bound AP-1. Here we report on the molecular mechanism by which nTRIP6 exerts these effects. Both the LIM domains and the pre-LIM region of nTRIP6 are necessary for its co-activator function for AP-1. Discrete domains within the pre-LIM region mediate the dimerization of nTRIP6 at the promoter, which enables the recruitment of the Mediator complex subunits THRAP3 and Med1. This recruitment is blocked by GR, through a competition between GR and THRAP3 for the interaction with the LIM domains of nTRIP6. Thus, nTRIP6 both positively and negatively regulates transcription by orchestrating the recruitment of the Mediator complex to AP-1-regulated promoters.
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影响因子：
16
作者：
Beli, Petra;Lukashchuk, Natalia;Wagner, Sebastian A.;Weinert, Brian T.;Olsen, Jesper V.;Baskcomb, Linda;Mann, Matthias;Jackson, Stephen P.;Choudhary, Chunaram
通讯作者：
Choudhary, Chunaram
影响因子：
64.8
作者：
Bannister, AJ;Kouzarides, T
通讯作者：
Kouzarides, T
影响因子：
14.9
作者：
CORPET, F
通讯作者：
CORPET, F
DOI：
10.1083/jcb.200309159
发表时间：
2004-02-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Akazawa H;Kudoh S;Mochizuki N;Takekoshi N;Takano H;Nagai T;Komuro I
通讯作者：
Komuro I
影响因子：
16
作者：
Ito, M;Yuan, CX;Roeder, RG
通讯作者：
Roeder, RG