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首页> 外文期刊>Cell cycle >Identification of a functional nuclear export sequence in diacylglycerol kinase-zeta.
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Identification of a functional nuclear export sequence in diacylglycerol kinase-zeta.

机译：二酰基甘油激酶-zeta中功能性核输出序列的鉴定。

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摘要

Diacylglycerol kinases (DGKs) are key regulators of diacylglycerol-dependent signaling pathways. Among the 10 DGK isoforms, DGK-zeta is the only nuclear form that contains a nuclear localization signal. Here, by site-directed mutagenesis, we showed that DGK-zeta also displays a functional independent nuclear export signal (NES) sequence between the amino acid residues 362-370. Indeed, the NES mutant forms of DGK-zeta accumulated in the nucleus to a much greater extent than wildtype DGK-zeta. Moreover, treatment with leptomycin B, an inhibitor of leucine-rich type NES, resulted in accumulation of both endogenous and ectopically expressed DGK-zeta in the nucleus, demonstrating that nuclear export of DGK-zeta is chromosome regional maintenance protein 1 (CRM1)-dependent. Previously, we reported that nuclear DGK-zeta is a negative regulator of cell cycle progression in C2C12 mouse myoblasts. In this paper, we documented that enhancement of DGK-zeta nuclear localization by NES sequence mutation, increases G(0)/G(1) block in C2C12 cells. Overall, our data demonstrate that DGK-zeta export from nucleus to cytoplasm is regulated by a leucine-rich NES through the exportin CRM1 and suggest that the nuclear localization of DGK-zeta could finely tune its function as a regulator of G(1)/S cell cycle transition.
机译：二酰基甘油激酶（DGK）是二酰基甘油依赖性信号通路的关键调节剂。在这10种DGK异构体中，DGK-zeta是唯一包含核定位信号的核形式。在这里，通过定点诱变，我们显示DGK-zeta在氨基酸残基362-370之间还显示了功能独立的核输出信号（NES）序列。确实，DGK-zeta的NES突变体形式比野生型DGK-zeta更大地积累在细胞核中。此外，使用富含亮氨酸的NES抑制剂瘦霉素B导致内源性和异位表达的DGK-zeta在核中蓄积，这表明DGK-zeta的核输出是染色体区域维持蛋白1（CRM1）-依赖。以前，我们报道了核DGK-zeta是C2C12小鼠成肌细胞中细胞周期进程的负调控因子。在本文中，我们记录了通过NES序列突变增强DGK-zeta核定位，增加了C2C12细胞中的G（0）/ G（1）阻滞。总体而言，我们的数据表明，DGK-zeta从细胞核向细胞质的出口受富含亮氨酸的NES通过Exportin CRM1的调节，并表明DGK-zeta的核定位可以很好地调节其作为G（1）/ S细胞周期过渡。

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