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首页> 外文期刊>Molecular and Cellular Biology >Interaction and Functional Cooperation between the LIM Protein FHL2, CBP/p300, and β-Catenin
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Interaction and Functional Cooperation between the LIM Protein FHL2, CBP/p300, and β-Catenin

机译：LIM蛋白FHL2，CBP / p300和β-连环蛋白之间的相互作用和功能合作

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Transcriptional activation of gene expression by Wnt signaling is driven by the association of β-catenin with TCF/LEF factors and the recruitment of transcriptional coactivators. It has been shown that the LIM protein FHL2 and the acetyltransferase CBP/p300 individually stimulate β-catenin transactivating activity and that β-catenin is acetylated by p300. Here, we report that FHL2 and CBP/p300 synergistically enhanced β-catenin/TCF-mediated transcription from Wnt-responsive promoters and that the acetyltransferase activity of CBP/p300 was involved in the cooperation. CBP/p300 interacted directly with FHL2, predominantly through the CH3 domain but not the histone acetyltransferase domain, and different regions of CBP/p300 were involved in FHL2 and β-catenin binding. We provided evidence for the formation of a ternary complex by FHL2, CBP/p300, and β-catenin and for colocalization of the three proteins in the nucleus. In murine FHL2?/? embryo fibroblasts, the transactivation activity of β-catenin/TCF was markedly reduced, and this defect could be restored by exogenous expression of FHL2. However, CBP/p300 were still able to coactivate the β-catenin/TCF complex in FHL2?/? cells, suggesting that FHL2 is dispensable for the coactivator function of CBP/p300 on β-catenin. Furthermore, we found that FHL2 significantly increased acetylation of β-catenin by p300 in vivo. Finally, we showed that FHL2, CBP/p300, and β-catenin could synergistically activate androgen receptor-mediated transcription, indicating that the synergistic coactivator function is not restricted to TCF/LEF.
机译：β-catenin与TCF / LEF因子的结合以及转录共激活因子的募集驱动着Wnt信号对基因表达的转录激活。已经显示LIM蛋白FHL2和乙酰转移酶CBP / p300分别刺激β-连环蛋白的反式激活活性，并且β-连环蛋白被p300乙酰化。在这里，我们报道FHL2和CBP / p300协同增强了Wnt反应性启动子的β-catenin/ TCF介导的转录，并且CBP / p300的乙酰转移酶活性参与了合作。 CBP / p300主要通过CH3结构域与组蛋白乙酰转移酶结构域直接相互作用，主要通过CH3结构域，而CBP / p300的不同区域参与FHL2和β-catenin的结合。我们提供了由FHL2，CBP / p300和β-catenin形成三元复合物以及在细胞核中这三种蛋白质共定位的证据。在小鼠FHL2 ？/？胚胎成纤维细胞中，β-catenin/ TCF的反式激活活性显着降低，该缺陷可以通过外源表达FHL2来修复。然而，CBP / p300仍然能够在FHL2 ？/？细胞中共激活β-catenin/ TCF复合物，提示FHL2对于CBP / p300对β-catenin的共激活功能是不可或缺的。此外，我们发现FHL2在体内显着增加了p300对β-catenin的乙酰化作用。最后，我们表明FHL2，CBP / p300和β-catenin可以协同激活雄激素受体介导的转录，表明协同辅激活功能不限于TCF / LEF。

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