Synergistic roles of Hs1VU and other ATP-dependent proteases in controlling in vivo turnover of sigma(32) and abnormal proteins in Escherichia coli
Synergistic roles of Hs1VU and other ATP-dependent proteases in controlling in vivo turnover of sigma(32) and abnormal proteins in Escherichia coli
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DOI：
10.1128/jb.179.23.7219-7225.1997
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发表时间：
1997-12-01
影响因子：
3.2
通讯作者：
Yura, T
中科院分区：
文献类型：
--
作者：
Kanemori, M;Nishihara, K;Yura, T
稳态生长期间异常蛋白质的产生通过稳定通常不稳定的sigma（32）（由rpoH基因编码）诱导热休克反应，所述sigma（32）是热休克基因转录特异性所需的。我们在这里报告，携带hslVU操纵子编码一种新的ATP依赖性蛋白酶的多拷贝质粒抑制大肠杆菌中的人尿激酶原（proUK）的生产诱导的热休克反应。HslVU（ClpQY）蛋白酶的过量产生显著降低proUK的稳定性和积累，从而减少热休克蛋白的诱导。与该发现一致，染色体hslVU基因的缺失显著提高了proUK和σ的水平（32），而没有明显影响细胞生长。当Δ hslVU缺失与另一种蛋白酶突变（loll、clpP或ftsH/hflB）组合时，所得的多个突变引起proUK和sigma的更高稳定性（32）、热休克蛋白的合成增强和温度敏感性生长。此外，HslVU蛋白酶的过量产生降低了菌株中的σ（32）水平，否则由于Lon-ClpXP蛋白酶的不存在或FtsH蛋白酶的限制水平，预期这些菌株产生增强水平的σ（32）。因此，一组ATP依赖性蛋白酶似乎通过调节σ（32）的体内周转以及通过降解异常蛋白质在热休克反应的负控制中发挥协同作用。
Production of abnormal proteins during steady-state growth induces the heat shock response by stabilizing normally unstable sigma(32) (encoded by the rpoH gene) specifically required for transcription of heat shock genes. We report here that a multicopy plasmid carrying the hslVU operon encoding a novel ATP-dependent protease inhibits the heat shock response induced by production of human prourokinase (proUK) in Escherichia coli. The overproduction of HslVU (ClpQY) protease markedly reduced the stability and accumulation of proUK and thus reduced the induction of heat shock proteins. In agreement with this finding, deletion of the chromosomal hslVU genes significantly enhanced levels of proUK and sigma(32) without appreciably affecting cell growth. When the Delta hslVU deletion was combined with another protease mutation (loll, clpP, or ftsH/hflB), the resulting multiple mutations caused higher stabilization of proUK and sigma(32), enhanced synthesis of heat shock proteins, and temperature-sensitive growth. Furthermore, overproduction of HslVU protease reduced sigma(32) levels in strains that were otherwise expected to produce enhanced levels of sigma(32) due either to the absence of Lon-ClpXP proteases or to the limiting levels of FtsH protease. Thus, a set of ATP-dependent proteases appear to play synergistic roles in the negative control of the heat shock response by modulating in vivo turnover of sigma(32) as well as through degradation of abnormal proteins.