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首页> 外文期刊>The FEBS journal >Glutamine stimulates the gene expression and processing of sterol regulatory element binding proteins, thereby increasing the expression of their target genes
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Glutamine stimulates the gene expression and processing of sterol regulatory element binding proteins, thereby increasing the expression of their target genes

机译:谷氨酰胺刺激固醇调节元件结合蛋白的基因表达和加工,从而增加其靶基因的表达

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Here we show that the larger the amount of glutamine added to the medium, the more the expression of genes related to lipid homeostasis is promoted by the activation of sterol regulatory element binding proteins (SREBPs) at the transcriptional and post-translational levels in human hepatoma HepG2 cells. Glutamine increases the mRNA levels of several SREBP targets, including SREBP-2. The gene expression of SREBP-1a, a predominant form of SREBP-1 in most cultured cells and a target of the general transcription factor Sp1, is significantly augmented by glutamine via an increased binding of Sp1 to the SREBP-1a promoter. In contrast, the increased expression of SREBP targets including SREBP-2 is due to stimulation of the processing of SREBP proteins by glutamine. It is also shown that glutamine accelerates SREBP processing through increased transport of the SREBP/SREBP cleavage-activating protein complex from the endoplasmic reticulum to the Golgi apparatus. The processing of activating transcription factor 6 is activated by the same proteases as SREBPs in the Golgi in response to endoplasmic reticulum stress and is not induced by glutamine. Taken together, these results clearly demonstrate that glutamine brings about not only the induction of SREBP-1a transcription but also the stimulation of SREBP processing, thereby facilitating the gene expression of SREBP targets in cultured cells.
机译:在这里我们显示,添加到培养基中的谷氨酰胺数量越多,在人类肝癌的转录和翻译后水平上,固醇调节元件结合蛋白(SREBPs)的激活会促进与脂质稳态相关的基因的表达。 HepG2细胞。谷氨酰胺增加了包括SREBP-2在内的几个SREBP靶标的mRNA水平。谷氨酰胺通过Sp1与SREBP-1a启动子的结合增强,显着增强了SREBP-1a的基因表达,SREBP-1a是大多数培养细胞中SREBP-1的主要形式,也是一般转录因子Sp1的靶标。相反,包括SREBP-2的SREBP靶标的表达增加是由于谷氨酰胺刺激SREBP蛋白的加工。还显示出谷氨酰胺通过增加SREBP / SREBP裂解活化蛋白复合物从内质网向高尔基体的运输而加速了SREBP的加工。响应于内质网应激,激活转录因子6的加工被高尔基体中与SREBPs相同的蛋白酶激活,而不被谷氨酰胺诱导。综上,这些结果清楚地表明,谷氨酰胺不仅引起SREBP-1a转录的诱导,而且引起SREBP加工的刺激,从而促进培养细胞中SREBP靶标的基因表达。

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