Liu Xin Yu, Seh Cheah Chen, Cheung Peter C F
Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
FEBS Lett. 2008 Dec 10;582(29):4023-31. doi: 10.1016/j.febslet.2008.10.053. Epub 2008 Nov 19.
The protein kinase transforming-growth-factor-beta-activated kinase-1 (TAK1) is a key regulator in the pro-inflammatory signaling pathway and is activated by tumor necrosis factor-alpha, interleukin-1 (IL-1) and lipopolysaccharide (LPS). We describe the identification of TAK1 as a client protein of the 90 kDa heat-shock protein (Hsp90)/cell division cycle protein 37 (Cdc37) chaperones. However, Hsp90 is not required for the activation of TAK1 as short exposure to the Hsp90 inhibitor, 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) did not affect its activation by LPS or IL-1. Prolonged treatment of cells with 17-AAG inhibits Hsp90 and downregulates TAK1. Our results suggest that Hsp90 is required for the folding and stability of TAK1 but is displaced and no longer required when TAK1 is complexed to TAK1-binding protein-1 (TAB1).
蛋白激酶转化生长因子-β激活激酶1（TAK1）是促炎信号通路中的关键调节因子，可被肿瘤坏死因子-α、白细胞介素-1（IL-1）和脂多糖（LPS）激活。我们描述了TAK1作为90 kDa热休克蛋白（Hsp90）/细胞分裂周期蛋白37（Cdc37）伴侣蛋白的一种客户蛋白的鉴定。然而，Hsp90对于TAK1的激活并非必需，因为短期暴露于Hsp90抑制剂17-（烯丙基氨基）-17-去甲氧基格尔德霉素（17-AAG）并不影响其被LPS或IL-1激活。用17-AAG长时间处理细胞会抑制Hsp90并下调TAK1。我们的结果表明，Hsp90对于TAK1的折叠和稳定性是必需的，但当TAK1与TAK1结合蛋白-1（TAB1）形成复合物时，Hsp90会被取代且不再被需要。
