Mechanism and function of a novel stress-induced nuclear import pathway

在细胞热应激过程中，分子伴侣蛋白HSP70的核输入量上调。然而，HSP70在细胞核中的转运机制和生理意义尚不清楚。利用热应激条件下的体外转运系统，我们发现了一种名为Hikeshi的新型核导入载体，它介导热应激诱导的HSP70核导入。与进口蛋白- β家族介导的核转运不同，hikishi介导的HSP70核进口与HSP70的atp酶周期相耦合。在人类活细胞中，hikishi的消耗降低了细胞在热应激条件下恢复的活力，并显著延迟了热应激反应的衰减和恢复。核HSP70部分缓解了hikishi -depletion的效应，说明HSP70通过作用于细胞核来抵消热应力损伤。

Nuclear import of molecular chaperones HSP70 is up-regulated during cellular thermal stresses. However, the mechanism of nuclear transport and physiological significance of HSP70 in the nucleus remains to be unknown. Using our in vitro transport system under heat stress conditions, we identified a novel nuclear import carrier named Hikeshi that mediates heat-stress-induced nuclear import of HSP70. Unlike importin-beta-family-mediated nuclear transport, the Hikeshi-mediated nuclear import of HSP70 is coupled with the ATPase cycle of HSP70. In human living cells, depletion of Hikeshi reduces cell viability during recovery from heat stress conditions, and delays the attenuation and reversion of the heat stress response significantly. Nuclear HSP70 rescues the effect of Hikeshi-depletion partially, suggesting that HSP70 counteracts to the heat stress damages by acting in the nucleus.