Clients and Oncogenic Roles of Molecular Chaperone gp96/grp94.
Clients and Oncogenic Roles of Molecular Chaperone gp96/grp94.
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DOI：
10.2174/1568026616666160413141613
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发表时间：
2016
影响因子：
3.4
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Ansa-Addo EA;Thaxton J;Hong F;Wu BX;Zhang Y;Fugle CW;Metelli A;Riesenberg B;Williams K;Gewirth DT;Chiosis G;Liu B;Li Z
糖蛋白（gp） 96是一种内质网热休克蛋白（HSP） 90副对话体，通过伴随抗原肽活化T细胞而具有免疫特性。近十年来的遗传学研究表明，gp96也是toll样受体（TLRs）、整合素、Wnt共受体、低密度脂蛋白受体相关蛋白6 （LRP6）、潜在TGFβ对接受体、糖蛋白A重复显性（GARP）、糖蛋白（GP） Ib和胰岛素样生长因子（IGF）等多种受体和分泌蛋白的重要主伴侣蛋白。临床上，gp96在多种癌症中的表达升高与癌症患者的晚期和较差的生存期相关。最近的临床前研究还发现，gp96的表达与多发性骨髓瘤、肝细胞癌、乳腺癌和炎症相关结肠癌的癌症进展密切相关。因此，gp96是一个有吸引力的癌症治疗靶点。gp96的伴侣功能取决于其atp酶结构域，该结构域在结构上与其他HSP90成员不同，因此有利于设计高选择性的gp96靶向癌症抑制剂。我们在此讨论gp96的战略上重要的致癌客户及其潜在的生物学。细胞内固有的gp96在T细胞生物学中的作用也被讨论，部分原因是它通过控制T细胞中gp96的水平来增强宿主免疫防御，为癌症治疗提供了另一个机会。
As an endoplasmic reticulum heat shock protein (HSP) 90 paralogue, glycoprotein (gp) 96 possesses immunological properties by chaperoning antigenic peptides for activation of T cells. Genetic studies in the last decade have unveiled that gp96 is also an essential master chaperone for multiple receptors and secreting proteins including Toll-like receptors (TLRs), integrins, the Wnt co-receptor, Low Density Lipoprotein Receptor-Related Protein 6 (LRP6), the latent TGFβ docking receptor, Glycoprotein A Repetitions Predominant (GARP), Glycoprotein (GP) Ib and insulin-like growth factors (IGF). Clinically, elevated expression of gp96 in a variety of cancers correlates with the advanced stage and poor survival of cancer patients. Recent preclinical studies have also uncovered that gp96 expression is closely linked to cancer progression in multiple myeloma, hepatocellular carcinoma, breast cancer and inflammation-associated colon cancer. Thus, gp96 is an attractive therapeutic target for cancer treatment. The chaperone function of gp96 depends on its ATPase domain, which is structurally distinct from other HSP90 members, and thus favors the design of highly selective gp96-targeted inhibitors against cancer. We herein discuss the strategically important oncogenic clients of gp96 and their underlying biology. The roles of cell-intrinsic gp96 in T cell biology are also discussed, in part because it offers another opportunity of cancer therapy by manipulating levels of gp96 in T cells to enhance host immune defense.
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影响因子：
4.4
作者：
Binder, RJ;Anderson, KM;Srivastava, PK
通讯作者：
Srivastava, PK
影响因子：
4.4
作者：
Dai, Jie;Liu, Bei;Li, Zihai
通讯作者：
Li, Zihai
影响因子：
64.5
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
通讯作者：
CHERESH, DA
DOI：
10.1084/jem.189.9.1437
发表时间：
1999-05-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chandawarkar RY;Wagh MS;Srivastava PK
通讯作者：
Srivastava PK
影响因子：
32.4
作者：
Basu, S;Binder, RJ;Srivastava, PK
通讯作者：
Srivastava, PK