Department of Chemistry and Biochemistry, California State University Long Beach, CA, USA.
Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA.
FEBS Lett. 2020 Mar;594(6):1088-1100. doi: 10.1002/1873-3468.13685. Epub 2019 Nov 30.
Cell surface translocation of the chaperone glucose-regulated protein 78 kDa (GRP78) is a key event that promotes cancer cell survival during endoplasmic reticulum (ER) stress. Here, we identify Gα-interacting vesicle-associated protein (GIV) - an enhancer of prosurvival signaling during ER stress - as a binding partner of GRP78. We show that GIV and GRP78 interact in an ER stress-dependent manner through their respective carboxyl terminal domains and that GIV aids in the localization of GRP78 to the plasma membrane. Kaplan-Meier analysis of disease-free survival in cancer patients shows poor prognosis for patients with high expression of both GIV and GRP78, further suggesting a vital role for these two proteins in enhancing cancer cell viability.
细胞表面伴侣葡萄糖调节蛋白 78 kDa（GRP78）易位是促进内质网（ER）应激期间癌细胞存活的关键事件。在这里，我们确定 G 蛋白相互作用的囊泡相关蛋白（GIV） - ER 应激期间促进生存信号的增强子 - 作为 GRP78 的结合伴侣。我们表明，GIV 和 GRP78 通过它们各自的羧基末端结构域以 ER 应激依赖的方式相互作用，并且 GIV 有助于 GRP78 定位于质膜。对癌症患者无病生存的 Kaplan-Meier 分析表明，GIV 和 GRP78 表达均高的患者预后不良，这进一步表明这两种蛋白在增强癌细胞活力方面起着至关重要的作用。
