Proteasome inhibitors MG132 and lactacystin hyperphosphorylate HSF1 and induce hsp70 and hsp27 expression
Proteasome inhibitors MG132 and lactacystin hyperphosphorylate HSF1 and induce hsp70 and hsp27 expression
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DOI：
10.1006/bbrc.1998.9840
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发表时间：
1999-01-08
影响因子：
3.1
通讯作者：
Li, GC
中科院分区：
文献类型：
--
作者：
Kim, D;Kim, SH;Li, GC
MG132和lactacystin是两种26S蛋白酶体特异性蛋白酶抑制剂，可以在不发生热休克的情况下上调热休克基因转录。在这项研究中，我们发现这两种抑制剂在没有热激（37°C）的情况下诱导 HSF1 的过度磷酸化和 DNA 结合活性。由于三聚化；已知 HSF1 的磷酸化先于 HSF1-DNA 结合活性的获得，似乎 MG132 和乳胞素诱导的 HSF1 过度磷酸化会导致 HSF1 分子在 37°C 下发生构象变化，随后触发其三聚化。放线菌酮对蛋白质合成的抑制消除了 MG132 或乳胞素诱导的 HSF1 过度磷酸化和 DNA 结合活性。这些数据表明，在 MG132 或乳胞素存在的情况下，假定的针对 HSF1 的激酶的活性上调。激酶活性的上调需要从头合成蛋白质，并且可能是由于通过泛素-蛋白酶体途径抑制了针对 HSF1 的短寿命激酶和/或激酶的辅因子的蛋白质降解。 (C) 1999 年学术出版社。
MG132 and lactacystin, two 26S proteasome-specific protease inhibitors, can upregulate heat-shock gene transcription without heat shock. In this study, we showed that both of these inhibitors induce hyperphosphorylation and DNA-binding activity of HSF1 in the absence of heat shock (at 37 degrees C). Since trimerization; of HSF1 is known to precede the acquisition of HSF1-DNA binding activity, it seems that MG132- and lactacystin-induced hyperphosphorylation of HSF1 causes conformational changes of HSF1 molecules at 37 degrees C and subsequently triggers its trimerization. Inhibition of protein synthesis by cycloheximide abolished the MG132- or lactacystin-induced hyperphosphorylation and DNA-binding activity of HSF1. These data suggest that the activity of a putative kinase(s) targeting HSF1 is upregulated in the presence of MG132 or lactacystin. The upregulation of the kinase activity requires de novo protein synthesis and is likely due to the inhibition of protein degradation of a short-lived, kinase(s) targeting HSF1 and/or the cofactor(s) for the kinases, through the ubiquitin-proteasome pathway. (C) 1999 Academic Press.