The Par-4-GRP78 TRAIL, more twists and turns.
The Par-4-GRP78 TRAIL, more twists and turns.
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DOI：
10.4161/cbt.8.22.10140
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发表时间：
2009-11
影响因子：
3.6
通讯作者：
Lee AS
中科院分区：
文献类型：
--
作者：
Lee AS
GRP78，也称为 BiP，是一种重要的分子伴侣，也是未折叠蛋白反应的主要调节因子。传统上，GRP78 被认为定位于内质网 (ER) 的腔内。然而，最近的研究结果表明，GRP78 的一个亚组分可以定位于特定细胞类型的表面。此外，GRP78 在肿瘤细胞表面优先表达，但在正常器官中不表达，表明表面 GRP78 既可以作为癌症特异性治疗的靶点，也可以作为介质。最近的报告进一步证实，GRP78 与细胞表面的特定蛋白质形成复合物，并在信号传导、影响细胞存活和增殖中发挥重要作用。布里哈诺夫等人。 (Cell 2009, 138:377-88) 报道，Par-4 通常被认为是一种胞质和核蛋白，通过线粒体细胞死亡途径促进细胞死亡，由正常细胞和癌细胞自发分泌，并且该过程通过 ER 应激或添加 TRAIL 得到增强。据认为，由TRAIL等细胞外损伤引起的内质网应激，导致Par-4-GRP78复合物从内质网易位至质膜，并通过正反馈回路，细胞外Par-4与细胞表面GRP78结合并激活外源性凋亡途径。在这个期刊俱乐部中，我们讨论了一些悬而未决的问题，以及这些新发现如何与目前对 GRP78 体内功能的理解相结合。
GRP78, also referred to as BiP, is an essential molecular chaperone and a master regulator of the unfolded protein response. Traditionally, GRP78 is regarded as localized in the lumen of the endoplasmic reticulum (ER). However, recent findings revealed that a subfraction of GRP78 can localize to the surface of specific cell types. Furthermore, preferential expression of GRP78 on the surface of tumor cells but not in normal organs suggests that surface GRP78 can serve both as a target as well as mediator for cancer-specific therapy. Recent reports further established that GRP78 forms complexes with specific proteins on the cell surface and plays an important role in signaling, impacting cell survival and proliferation. Burikhanov et al. (Cell 2009, 138:377-88) reported that Par-4, generally regarded as a cytosolic and nuclear protein that promotes cell death via the mitochondrial cell death pathway, is spontaneously secreted by normal and cancer cells and this process is enhanced by ER stress or with addition of TRAIL. It is proposed that ER stress, induced by extracellular insults such as TRAIL, causes translocation of the Par-4-GRP78 complex from the ER to the plasma membrane, and through a positive feedback loop, extracellular Par-4 binds to cell surface GRP78 and activates the extrinsic apoptotic pathway. In this journal club, we discuss some open questions and how these new findings integrate with current understanding of GRP78 function in vivo.
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影响因子：
11.2
作者：
Fu, Yong;Li, Jianze;Lee, Amy S.
通讯作者：
Lee, Amy S.
DOI：
10.1073/pnas.0807691105
发表时间：
2008-12-09
影响因子：
11.1
作者：
Fu, Yong;Wey, Shiuan;Lee, Amy S.
通讯作者：
Lee, Amy S.
影响因子：
4.8
作者：
Reddy, RK;Mao, CH;Lee, AS
通讯作者：
Lee, AS
影响因子：
20.3
作者：
Kern, Johann;Untergasser, Gerold;Steurer, Michael
通讯作者：
Steurer, Michael
影响因子：
50.3
作者：
Arap, MA;Lahdenranta, J;Pasqualini, R
通讯作者：
Pasqualini, R