Proteasome inhibition leads to the activation of all members of the heat-shock-factor family
Proteasome inhibition leads to the activation of all members of the heat-shock-factor family
复制标题
DOI：
10.1046/j.1432-1327.1998.2550356.x
复制
发表时间：
1998-07-15
期刊：
影响因子：
--
通讯作者：
Nagata, K
中科院分区：
文献类型：
--
作者：
Kawazoe, Y;Nakai, A;Nagata, K
热休克蛋白和分子伴侣参与多种细胞代谢过程，包括蛋白质的合成和降解。当这些代谢过程受到干扰时，这些表达在转录水平上通过异常蛋白质的积累而升高。最近的研究表明，热休克蛋白的诱导是由蛋白酶体介导的。阐明这种诱导的机制。我们检测了禽类细胞中蛋白酶体抑制剂对热休克转录因子的激活。两种热休克诱导因子的激活。通过用蛋白酶体抑制剂处理细胞产生HSF 1和HSF 3。这种激活不是通过用各种其他蛋白酶抑制剂处理产生的。在蛋白质合成抑制剂放线菌酮存在下，蛋白酶体抑制剂对HSF的激活被完全阻断。出乎意料的是，发育相关因子HSF 2也被蛋白酶体抑制剂激活，其蛋白水平增加。这些结果表明，泛素-蛋白酶体途径可能通过控制HSF的某些调节因子或HSF本身的水平以及控制异常蛋白来调节所有三种HSF。
Heat-shock proteins and molecular chaperones are involved in various cellular metabolic processes including protein synthesis and degradation. These expressions are elevated at the level of transcription by the accumulation of abnormal proteins when these metabolic processes are disturbed. Recent works suggest the induction of heat-shock proteins by the inhibiton of proteasome. To elucidate the mechanism of this induction. we examined the activation of heat-shock transcription factors by proteasome inhibitors in avian cells. Activation of the two heat-shock-inducible factors. HSF1 and HSF3, was produced by the treatment of cells with proteasome inhibitors. This activation was not produced by treatment with various other protease Inhibitors, The HSF activation by proteasome inhibitors was completely blocked in the presence of the protein synthesis inhibitor cycloheximide. Unexpectedly, the development-related factor HSF2 was also activated by proteasome inhibitors, with an increase in its protein level. These results suggest that the ubiqutin-proteasome pathway may regulate all of the three HSFs by controlling the level of some regulatory factor for HSF or HSF itself as well as controlling abnormal proteins.