Alternative approaches to Hsp90 modulation for the treatment of cancer.
Alternative approaches to Hsp90 modulation for the treatment of cancer.
复制标题
DOI：
10.4155/fmc.14.89
复制
发表时间：
2014-09
影响因子：
4.2
通讯作者：
Blagg BS
中科院分区：
文献类型：
--
作者：
Hall JA;Forsberg LK;Blagg BS
Hsp90负责新合成多肽（客户蛋白）的构象成熟和变性蛋白通过Hsp90伴侣蛋白循环的再成熟。抑制热休克蛋白90 n端已成为抗癌化疗药物的临床相关策略，因为客户参与多种致癌途径。几种亲免疫蛋白、共伴侣蛋白和伴侣蛋白也是Hsp90陪伴活性所必需的。抑制Hsp90功能的其他策略包括破坏c端二聚化结构域和Hsp90异蛋白复合物。c端抑制剂和Hsp90共伴侣干扰物类似于n端抑制剂阻止癌细胞增殖，在不诱导热休克蛋白的情况下破坏客户蛋白的稳定。本文将讨论当前的Hsp90抑制剂、伴侣蛋白周期以及该周期的调控。
Hsp90 is responsible for the conformational maturation of newly synthesized polypeptides (client proteins) and the re-maturation of denatured proteins via the Hsp90 chaperone cycle. Inhibition of the Hsp90 N-terminus has emerged as a clinically relevant strategy for anticancer chemotherapeutics due to the involvement of clients in a variety of oncogenic pathways. Several immunophilins, co-chaperones and partner proteins are also necessary for Hsp90 chaperoning activity. Alternative strategies to inhibit Hsp90 function include disruption of the C-terminal dimerization domain and the Hsp90 heteroprotein complex. C-terminal inhibitors and Hsp90 co-chaperone disruptors prevent cancer cell proliferation similar to N-terminal inhibitors and destabilize client proteins without induction of heat shock proteins. Herein, current Hsp90 inhibitors, the chaperone cycle, and regulation of this cycle will be discussed.
登录
查看更多内容
影响因子：
4
作者：
Ardi, Veronica C.;Alexander, Leslie D.;Johnson, Victoria A.;McAlpine, Shelli R.
通讯作者：
McAlpine, Shelli R.
影响因子：
7.3
作者：
Brandt GE;Schmidt MD;Prisinzano TE;Blagg BS
通讯作者：
Blagg BS
影响因子：
21.3
作者：
Connell, P;Ballinger, CA;Patterson, C
通讯作者：
Patterson, C
影响因子：
4.8
作者：
Bansal, Parmil K.;Mishra, Ashutosh;Kitagawa, Katsumi
通讯作者：
Kitagawa, Katsumi
DOI：
10.1124/jpet.105.088088
发表时间：
2005-10-01
影响因子：
3.5
作者：
Carbone, DL;Doorn, JA;Petersen, DR
通讯作者：
Petersen, DR