Heat shock protein 90 suppresses tumor necrosis factor alpha induced apoptosis by preventing the cleavage of Bid in NIH3T3 fibroblasts.
Heat shock protein 90 suppresses tumor necrosis factor alpha induced apoptosis by preventing the cleavage of Bid in NIH3T3 fibroblasts.
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DOI：
10.1016/j.cellsig.2003.08.005
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发表时间：
2004-03
影响因子：
4.8
通讯作者：
Chen Zhao;E. Wang
中科院分区：
文献类型：
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作者：
Chen Zhao;E. Wang
维持细胞内稳态的两种高度保守的机制是细胞凋亡和细胞应激反应。热休克蛋白90是真核生物中最丰富、最保守、最易诱导的热休克蛋白之一。近年来研究表明，Hsp 90通过与Apaf-1、RIP和IKK α/β的激酶结构域结合发挥重要的抗凋亡作用。我们目前的研究表明，热休克蛋白90可以抑制肿瘤坏死因子α（TNF α）诱导的细胞凋亡，在稳定的热休克蛋白90过表达的NIH 3 T3细胞，通过阻止Bid的切割。Hsp 90与Bid的直接相互作用可以部分解释Bid断裂的阻止。此外，通过加入其特异性抑制剂格尔德霉素来破坏Hsp 90的功能，阻断了Hsp 90对Bid切割的保护。这些结果表明，热休克蛋白90可以在不同水平的细胞凋亡信号转导途径中发挥作用。
Two highly conserved mechanisms for maintaining cellular homeostasis are apoptosis and the cellular stress response. Hsp90 is one of the most abundant, highly conserved, and inducible Hsps in eukaryotes. Recently, Hsp90 has been shown to play important antiapoptotic roles through binding with Apaf-1, RIP and kinase domain of IKKalpha/beta. Our present studies demonstrate that Hsp90 can suppress tumor necrosis factor alpha (TNFalpha)-induced apoptosis in stable Hsp90-overexpressing NIH3T3 cells by preventing the cleavage of Bid. The prevention of the cleavage of Bid can be partially explained by the direct interaction between Hsp90 and Bid. Furthermore, disrupting the function of Hsp90 by the addition of its specific inhibitor, geldanamycin, blocked Hsp90's protection of Bid cleavage. These results show that Hsp90 can function at different levels within apoptotic signal transduction pathways.