XBP1: a link between the unfolded protein response, lipid biosynthesis, and biogenesis of the endoplasmic reticulum.
XBP1: a link between the unfolded protein response, lipid biosynthesis, and biogenesis of the endoplasmic reticulum.
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DOI：
10.1083/jcb.200406136
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发表时间：
2004-10-11
期刊：
影响因子：
--
通讯作者：
Brewer JW
中科院分区：
文献类型：
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作者：
Sriburi R;Jackowski S;Mori K;Brewer JW
当挑战内质网（ER）的蛋白质折叠能力时，展开的蛋白质反应（UPR）通过调节蛋白质的合成并增强耐ER蛋白的表达来保持ER稳态，从而促进蛋白质成熟和降解。在这里，我们报告说，通过UPR介导的XBP1 mRNA剪接产生的XBP1转录因子的活性形式足以诱导磷脂酰胆碱，这是ER膜的初级磷脂的合成。过表达XBP1（S）的细胞表现出膜磷脂水平升高，表面积增加和粗糙ER的体积以及磷脂酰胆碱生物合成的胞苷二磷胆碱途径的增强。这些数据表明XBP1将哺乳动物UPR与磷脂生物合成和ER生物发生联系起来。
When the protein folding capacity of the endoplasmic reticulum (ER) is challenged, the unfolded protein response (UPR) maintains ER homeostasis by regulating protein synthesis and enhancing expression of resident ER proteins that facilitate protein maturation and degradation. Here, we report that enforced expression of XBP1(S), the active form of the XBP1 transcription factor generated by UPR-mediated splicing of XBP1 mRNA, is sufficient to induce synthesis of phosphatidylcholine, the primary phospholipid of the ER membrane. Cells overexpressing XBP1(S) exhibit elevated levels of membrane phospholipids, increased surface area and volume of rough ER, and enhanced activity of the cytidine diphosphocholine pathway of phosphatidylcholine biosynthesis. These data suggest that XBP1(S) links the mammalian UPR to phospholipid biosynthesis and ER biogenesis.