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首页> 外文期刊>Journal of Lipid Research >Apoptosis-induced release of mature sterol regulatory element-binding proteins activates sterol-responsive genes.
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Apoptosis-induced release of mature sterol regulatory element-binding proteins activates sterol-responsive genes.

机译:凋亡诱导的成熟固醇调节元件结合蛋白的释放激活了固醇响应基因。

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摘要

It is well established that during the execution of the apoptotic cascade, activated caspase 3 releases sterol regulatory element-binding proteins (SREBP) from the membrane of the endoplasmic reticulum in a proteolytic reaction that is distinct from their normal sterol-dependent activation. However, it is not known whether these transcription factors are capable of activating sterol-responsive genes under such conditions. The construction of SRE expression vectors has permitted characterization of the apoptotic activation of SREBP. Cell lines stably expressing the plasma membrane marker CD32, or GFP, under the control of the SRE promoter were shown to modulate SRE gene expression on the basis of the levels of available sterols. However, during the induction of apoptosis, expression of CD32 and GFP was highly induced, even in the presence of ample sterols. Apoptotic induction of sterol-regulated genes was due to activation of caspase 3 and was impervious to treatment with sphingomyelinase, indicating that activation of SRE genes during apoptosis is sterol independent. Further characterization of this apoptotic response indicated that sterol-regulated genes are activated at an early stage in the apoptotic cascade, preceding the externalization of phosphatidylserine on the plasma membrane of apoptotic cells. These results suggest that activation of sterol-responsive genes early during apoptosis may play a role in the proper execution of this program.
机译:公认的是,在执行凋亡级联反应期间,活化的半胱天冬酶3以不同于其正常固醇依赖性激活的蛋白水解反应从内质网膜释放固醇调节元件结合蛋白(SREBP)。然而,尚不清楚这些转录因子是否能够在这样的条件下激活固醇应答基因。 SRE表达载体的构建允许表征SREBP的凋亡激活。在SRE启动子的控制下,稳定表达质膜标记物CD32或GFP的细胞系显示可利用的固醇水平调节SRE基因的表达。然而,在诱导细胞凋亡期间,即使存在大量固醇,也高度诱导了CD32和GFP的表达。固醇调节基因的凋亡诱导归因于caspase 3的激活,并不受鞘磷脂酶处理的影响,这表明凋亡过程中SRE基因的激活与固醇无关。对该凋亡反应的进一步表征表明,在凋亡细胞质膜上的磷脂酰丝氨酸外化之前,固醇调节基因在凋亡级联的早期被激活。这些结果表明在凋亡过程中早期的固醇响应基因的激活可能在该程序的正确执行中起作用。

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