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首页> 外文期刊>The Journal of biological chemistry >Transducin-like Enhancer of Split-1 (TLE1) Combines with Forkhead Box Protein G1 (FoxG1) to Promote Neuronal Survival
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Transducin-like Enhancer of Split-1 (TLE1) Combines with Forkhead Box Protein G1 (FoxG1) to Promote Neuronal Survival

机译：Split-1（TLE1）的转霉素样增强剂与Forkhead盒蛋白G1（Foxg1）组合，以促进神经元生存率

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Transducin-like enhancer of split-1 (TLE1) plays a critical role in the regulation of neurogenesis by inhibiting the differentiation of neural progenitor cells into neurons. Although TLE1 is also expressed highly in the postnatal brain and through adulthood, its role in postmitotic neurons is not clear. Using cultures of cerebellar granule neurons, we show that expression of TLE1 is reduced in neurons primed to die. Reestablishment of elevated TLE1 levels by ectopic expression protects neurons from death, whereas suppression of TLE1 expression in otherwise healthy neurons induces cell death. These results show that TLE1 is necessary for the maintenance of neuronal survival. Experiments using pharmacological inhibitors as well as expression of point mutants indicate that phosphorylation of TLE1 by casein kinase-2 (CK2) at Ser-239 and Ser-253 is necessary for its survival-promoting activity. TLE1-mediated survival is also inhibited by pharmacological inhibition of PI3K-Akt signaling but not by inhibitors of Raf-MEK-ERK signaling or other molecules, including histone deacetylases, calcium calmodulin kinase, or CK1. The survival-promoting activity of TLE1 depends critically on interaction with FoxG1, another protein involved in the regulation of neurogenesis and shown previously to promote survival of postmitotic neurons. Likewise, the ability of FoxG1 to promote neuronal survival depends on TLE1. Taken together, our study demonstrates that TLE1 cooperates with FoxG1 to promote neuronal survival in a CK2- and PI3K-Akt-dependent manner.
机译：通过抑制神经祖细胞进入神经元的分化，分裂-1（TLE1）的转霉素样增强剂在神经发生的调节中起着关键作用。虽然TLE1也在产后脑中高度表达，并且通过成年期表示，其在后暗神经元的作用尚不清楚。使用小脑颗粒神经元的培养，我们表明TLE1的表达降低了初步灭绝的神经元。通过异位表达重新建立升高的TLE1水平保护神经元免死神经元，而抑制在其他健康神经元中的TLE1表达诱导细胞死亡。这些结果表明，TLE1是维持神经元生存的必要条件。使用药物抑制剂以及点突变体的表达的实验表明，在SER-239和SER-253处通过酪蛋白激酶-2（CK2）的TLE1的磷酸化对于其存活促进活性是必需的。通过PI3K-AKT信号传导的药理学抑制，但不是由RAF-MEK-ERK信号传导或其他分子的抑制剂，包括组蛋白脱乙酰酶，钙钙调素激酶或CK1的药理抑制，还抑制了TLE1介导的存活。 TLE1的存活促进活性主要取决于与FOXG1的相互作用，另一种涉及神经发生调节的蛋白质，并以前促进后暗症神经元的存活。同样，Foxg1促进神经元存活的能力取决于TLE1。我们的研究一起携带，表明TLE1与Foxg1合作，以促进CK2和PI3K-AKT依赖性方式的神经元生存。

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