Inhibition of proteasomes induces accumulation, phosphorylation, and recruitment of HSP27 and αB-crystallin to aggresomes
Inhibition of proteasomes induces accumulation, phosphorylation, and recruitment of HSP27 and αB-crystallin to aggresomes
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DOI：
10.1093/oxfordjournals.jbchem.a003139
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发表时间：
2002-04-01
影响因子：
2.7
通讯作者：
Kato, K
中科院分区：
文献类型：
--
作者：
Ito, H;Kamei, K;Kato, K
分子伴侣和泛素-蛋白酶体途径参与细胞内蛋白质的质量控制。在这项研究中，我们检测了小的热休克蛋白对蛋白酶体抑制剂的反应，以阐明它们在错误折叠的蛋白异常积累的条件下的作用。蛋白酶体抑制剂MG-132作用后，Hsp27和α-晶状体蛋白在可溶组分中积累，更显著的是，在不溶组分中积累。观察到HSP27和α-晶体蛋白的mRNAs表达增强，提示转录激活。在MG-132处理的细胞中，HSP27和α-晶状体蛋白的磷酸化增强，同时激活p38和p44/42 MAP激酶通路。免疫荧光分析显示，蛋白酶体抑制剂诱导U373 MG细胞形成侵袭体，HSP27和α-晶体蛋白被加入到侵袭体中。然而，这种积累在侵袭体中并不需要磷酸化。因此，当蛋白酶体活性被抑制时，HSP27和α-晶体蛋白在侵袭体中被增加、磷酸化和定位。
Molecular chaperones and the ubiquitin-proteasome pathway are known to participate in the quality control of proteins in cells. In this study, we examined the responses of small heat shock proteins to proteasome inhibitors to clarify their roles under conditions where misfolded proteins are abnormally accumulated. HSP27 and alphaB-crystallin accumulated in both soluble and, more prominently, insoluble fractions after exposure to MG-132, a proteasome inhibitor. Enhanced expression of mRNAs for HSP27 and alphaB-crystallin was observed, suggesting transcriptional activation. Phosphorylation of HSP27 and alphaB-crystallin in cells treated with MG-132 was enhanced concomitantly with activation of p38 and p44/42 MAP kinase pathways. Immunofluorescence analysis revealed that exposure to proteasome inhibitors induced the formation of aggresomes in U373 MG cells, to which HSP27 and alphaB-crystallin were recruited. However, phosphorylation was not required for this accumulation in aggresomes. Thus, HSP27 and alphaB-crystallin are increased, phosphorylated and localized in aggresomes when proteasome activity is inhibited.