Organismic functions of Trip6

Trip6是我们实验室分离到的糖皮质激素受体（GR）相互作用蛋白。它的c端一半携带三个LIM结构域，每个结构域定义不同的相互作用特异性。在LIM结构域的n端，Trip6携带一个二聚化序列。通过一个替代的翻译起始位点，它消除了核输出序列，但没有二聚化结构域，形成了核形式nTrip6。同二聚体的nTrip6结合启动子相关转录因子，如GR、Fos:Jun和p65-NF-(B)，并刺激转录。由于其多个相互作用域，nTrip6可以在dna结合因子之上组装额外的转录因子。这将复合体最频繁地转化为抑制模式，例如，当在Fos:Jun或NF-(B)上组装核激素受体时。通过这一作用，激活的GR抑制炎症过程。另一种可选择的3翻译产物从细胞核输出，并在局灶黏附处与质膜相关。它也同二聚体，与黏附复合物的其他几种蛋白质相互作用，并似乎受n端磷酸化的调节。因此，这两种形式都表现出不同的功能：nTrip6的转录调节，长形式的膜相关功能，如迁移、粘附和可能的肿瘤发生（见下文）。

Trip6 has been isolated in our laboratory as a glucocorticoid receptor (GR) interacting protein. It carries three LIM domains in its C-terminal half, each one of which defines different interaction specificities. N-terminal to the LIM domains Trip6 carries a dimerization sequence. By an alternative translational start site which eliminates a nuclear export sequence, but not the dimerization domain, a nuclear form, nTrip6, is formed. The homodimeric nTrip6 binds to promoter-associated transcription factors such as GR, Fos:Jun and p65-NF-(B, and stimulates transcription. Due to its several interaction domains nTrip6 can assemble additional transcription factors on top of the DNA-bound factor. This converts the complex most frequently into a repressing mode, e.g. when assembling a nuclear hormone receptor on top of Fos:Jun or NF-(B. By this action activated GR inhibits inflammatory processes. The other alternative 3 translational product is exported from the nucleus and is associated with the plasma membrane at focal adhesions. It also homodimerizes, interacts with several other proteins of the focal adhesion complex and appears to be regulated by phosphorylation of an N-terminal site. Both forms thus exhibit distinct functions: transcriptional regulation by nTrip6, membrane-associated functions such as migration, adhesion and possibly tumorigenesis (see later) by the long form.