Andrews G K, Harding M A, Calvet J P, Adamson E D
Department of Biochemistry, University of Kansas Medical Center, Kansas City 66103.
Mol Cell Biol. 1987 Oct;7(10):3452-8. doi: 10.1128/mcb.7.10.3452-3458.1987.
Several known inducers of the heat shock response (heat stress, arsenite, and heavy metals) were shown to cause a significant elevation of c-fos mRNA in HeLa cells. Heat stress resulted in a time- and temperature-dependent prolonged elevation in the level of c-fos mRNA, which was accompanied by increased translation of c-fos protein and its appearance in the nucleus. Elevated expression of c-fos during heat stress was paralleled by induction of hsp 70 mRNA, while levels of c-myc and metallothionein mRNAs declined. Treatment of HeLa cells with arsenite or heavy metals also resulted in increased levels of hsp 70, as well as c-fos mRNA. Although elevated expression of c-fos was prevented by inhibitors of RNA synthesis, analysis of relative rates of gene transcription showed that during heat stress there was a negligible change in c-fos transcription. Therefore, the enhanced expression of c-fos during the heat shock response is likely to occur primarily through posttranscriptional processes. Cycloheximide was also shown to significantly increase the c-fos mRNA level in HeLa cells. There results are consistent with the observation that these inducers of the heat shock response, as well as cycloheximide, repress protein synthesis and suggest that the increase in the level of c-fos mRNA is caused by an inhibition of protein synthesis. This supports the hypothesis that c-fos mRNA is preferentially stabilized under conditions which induce the heat shock response, perhaps by decreased synthesis of a short-lived protein which regulates c-fos mRNA turnover.
几种已知的热休克反应诱导剂（热应激、亚砷酸盐和重金属）已被证明可导致HeLa细胞中c-fos mRNA显著升高。热应激导致c-fos mRNA水平呈时间和温度依赖性的持续升高，同时伴随着c-fos蛋白翻译增加及其在细胞核中的出现。热应激期间c-fos表达升高的同时，hsp 70 mRNA也被诱导，而c-myc和金属硫蛋白mRNA水平下降。用亚砷酸盐或重金属处理HeLa细胞也会导致hsp 70以及c-fos mRNA水平升高。虽然RNA合成抑制剂可阻止c-fos表达升高，但对基因转录相对速率的分析表明，热应激期间c-fos转录变化可忽略不计。因此，热休克反应期间c-fos表达增强可能主要通过转录后过程发生。环己酰亚胺也被证明可显著提高HeLa细胞中c-fos mRNA水平。这些结果与热休克反应诱导剂以及环己酰亚胺抑制蛋白质合成的观察结果一致，并表明c-fos mRNA水平升高是由蛋白质合成抑制引起的。这支持了一种假说，即在诱导热休克反应的条件下，c-fos mRNA优先被稳定，可能是通过减少调节c-fos mRNA周转的短寿命蛋白的合成来实现的。
