GRP78 at the Centre of the Stage in Cancer and Neuroprotection.
GRP78 at the Centre of the Stage in Cancer and Neuroprotection.
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DOI：
10.3389/fnins.2017.00177
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发表时间：
2017
影响因子：
4.3
通讯作者：
Casas C
中科院分区：
文献类型：
--
作者：
Casas C
78kDa的葡萄糖调节蛋白GRP78，也称为BiP和HSP5a，是一种多功能蛋白，其活性远远超出其在内质网（ER）应激后在细胞中激活的未折叠蛋白反应（UPR）中众所周知的作用。这些新发现的大多数活性取决于它在细胞内的位置。GRP78主要位于内质网，但也在细胞质、线粒体、细胞核、质膜中被观察到，并且可被分泌，尽管它主要致力于参与内源性细胞保护过程。因此，GRP78可能控制未折叠蛋白反应和巨自噬，或者可能激活磷脂酰肌醇3 - 激酶（PI3K）/AKT促存活通路。GRP78影响肿瘤细胞如何存活、增殖以及产生化疗耐药性。在神经退行性变中，内源性神经保护机制常常不足或失调。肿瘤生物学的经验可能为我们提供关于在年龄相关的神经退行性变中如何增强内源性神经保护机制的线索。在此，GRP78的功能在细胞保护这同一枚硬币看似相反的两面——神经退行性变和癌症——的舞台中心被揭示出来。目的是进行全面且批判性的综述，这可能有助于指导未来的实验，以确定增强神经保护的干预措施。
The 78-kDa glucose-regulated protein GRP78, also known as BiP and HSP5a, is a multifunctional protein with activities far beyond its well-known role in the unfolded protein response (UPR) which is activated after endoplasmic reticulum (ER) stress in the cells. Most of these newly discovered activities depend on its position within the cell. GRP78 is located mainly in the ER, but it has also been observed in the cytoplasm, the mitochondria, the nucleus, the plasma membrane, and secreted, although it is dedicated mostly to engage endogenous cytoprotective processes. Hence, GRP78 may control either UPR and macroautophagy or may activated phosphatidylinositol 3-kinase (PI3K)/AKT pro-survival pathways. GRP78 influences how tumor cells survive, proliferate, and develop chemoresistance. In neurodegeneration, endogenous mechanisms of neuroprotection are frequently insufficient or dysregulated. Lessons from tumor biology may give us clues about how boosting endogenous neuroprotective mechanisms in age-related neurodegeneration. Herein, the functions of GRP78 are revealed at the center of the stage of apparently opposite sites of the same coin regarding cytoprotection: neurodegeneration and cancer. The goal is to give a comprehensive and critical review that may serve to guide future experiments to identify interventions that will enhance neuroprotection.