Role of HSP90 in Cancer.
Role of HSP90 in Cancer.
复制标题
热休克蛋白90在癌症中的作用
DOI：
10.3390/ijms221910317
复制
发表时间：
2021-09-25
影响因子：
5.6
通讯作者：
Lu Y
中科院分区：
文献类型：
--
作者：
Birbo B;Madu EE;Madu CO;Jain A;Lu Y
HSP 90是一种重要的分子伴侣蛋白，在所有生物体中都是保守的。作为伴侣蛋白，它正确折叠客户蛋白。在结构上，该蛋白是具有单体亚基的二聚体，所述单体亚基由三个主要保守结构域组成，所述三个主要保守结构域被称为N-末端结构域、中间结构域和C-末端结构域。HSP 90存在多种亚型，并且这些亚型具有高度同源性。这些同种型存在于细胞内和细胞外。HSP 90 α和HSP 90 β存在于细胞质中; TRAP 1存在于线粒体中; GRP 94存在于内质网中，可能由于翻译后修饰（PTM）而分泌。HSP 90也通过不同于经典分泌途径的外泌体途径分泌到细胞外环境中。多种辅助分子伴侣是HSP 90发挥功能所必需的。在癌症患者中观察到HSP 90水平升高。尽管如此，HSP 90在癌症中的可能作用被忽视了，因为伴侣蛋白在正常细胞中也存在极大量，并且对正常细胞功能至关重要，正如基因敲除导致的严重不良反应抑制这种蛋白质的产生时所观察到的那样。正常HSP 90和肿瘤表型的HSP 90之间的差异已被更好地理解，并有助于使伴侣蛋白成为癌症药物的靶点。一个不同之处在于构象：肿瘤表型的HSP 90对抑制剂更敏感。由于HSP 90的过表达是肿瘤发生的一个因素，因此已经研究了HSP 90抑制剂以对抗HSP 90过表达的不利影响。使用HSP 90抑制剂的单一疗法已经显示出一些成功;然而，联合疗法已经显示出更好的结果，因此正在研究更有效的癌症治疗。
HSP90 is a vital chaperone protein conserved across all organisms. As a chaperone protein, it correctly folds client proteins. Structurally, this protein is a dimer with monomer subunits that consist of three main conserved domains known as the N-terminal domain, middle domain, and the C-terminal domain. Multiple isoforms of HSP90 exist, and these isoforms share high homology. These isoforms are present both within the cell and outside the cell. Isoforms HSP90α and HSP90β are present in the cytoplasm; TRAP1 is present in the mitochondria; and GRP94 is present in the endoplasmic reticulum and is likely secreted due to post-translational modifications (PTM). HSP90 is also secreted into an extracellular environment via an exosome pathway that differs from the classic secretion pathway. Various co-chaperones are necessary for HSP90 to function. Elevated levels of HSP90 have been observed in patients with cancer. Despite this observation, the possible role of HSP90 in cancer was overlooked because the chaperone was also present in extreme amounts in normal cells and was vital to normal cell function, as observed when the drastic adverse effects resulting from gene knockout inhibited the production of this protein. Differences between normal HSP90 and HSP90 of the tumor phenotype have been better understood and have aided in making the chaperone protein a target for cancer drugs. One difference is in the conformation: HSP90 of the tumor phenotype is more susceptible to inhibitors. Since overexpression of HSP90 is a factor in tumorigenesis, HSP90 inhibitors have been studied to combat the adverse effects of HSP90 overexpression. Monotherapies using HSP90 inhibitors have shown some success; however, combination therapies have shown better results and are thus being studied for a more effective cancer treatment.
登录
查看更多内容
影响因子：
5.3
作者：
Cheng, Chieh-Fang;Fan, Jianhua;Li, Wei
通讯作者：
Li, Wei
DOI：
10.1186/bcr3168
发表时间：
2012-04-17
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Cheng Q;Chang JT;Geradts J;Neckers LM;Haystead T;Spector NL;Lyerly HK
通讯作者：
Lyerly HK
影响因子：
4.8
作者：
Dollins, DE;Immormino, RM;Gewirth, DT
通讯作者：
Gewirth, DT
影响因子：
8
作者：
Altieri, Dario C.
通讯作者：
Altieri, Dario C.
影响因子：
1.6
作者：
Dubey A;Prajapati KS;Swamy M;Pachauri V
通讯作者：
Pachauri V