DNA-BINDING OF HEAT-SHOCK FACTOR TO THE HEAT-SHOCK ELEMENT IS INSUFFICIENT FOR TRANSCRIPTIONAL ACTIVATION IN MURINE ERYTHROLEUKEMIA-CELLS
DNA-BINDING OF HEAT-SHOCK FACTOR TO THE HEAT-SHOCK ELEMENT IS INSUFFICIENT FOR TRANSCRIPTIONAL ACTIVATION IN MURINE ERYTHROLEUKEMIA-CELLS
复制标题
DOI：
10.1128/mcb.10.4.1600
复制
发表时间：
1990-04-01
影响因子：
5.3
通讯作者：
KINGSTON, RE
中科院分区：
文献类型：
--
作者：
HENSOLD, JO;HUNT, CR;KINGSTON, RE
热休克反应是调节基因表达的最高度保守的例子之一，存在于所有细胞生物体中。热休克基因的转录激活由升高的温度或其他细胞应激通过热休克因子（HSF）与存在于热诱导基因的启动子中的保守核苷酸序列（热休克元件）的结合来介导。尽管这种反应高度保守，但胚胎发育阶段的特征是没有热休克反应。小鼠红白血病（MEL）细胞也缺乏这种反应，我们在这里报告的一个最高度保守的这些基因，热休克蛋白70这种缺陷的详细特征。令人惊讶的是，尽管诱导了具有鼠HSF的结合特异性的蛋白质，但该基因的热诱导的转录激活并未发生。然而，MEL HSF在表观大小上与3T3细胞中的HSF略有不同，3T3细胞表现出正常的热休克反应。这些数据表明，激活哺乳动物HSF的热需要至少两个独立的步骤：结合活性的改变，然后进一步修改，激活转录。MEL细胞对热休克没有反应，因为它们缺乏进行这种二次修饰的能力。这些细胞提供了一个有用的系统，用于表征哺乳动物中的热储备激活。
The heat shock response is among the most highly conserved examples of regulated gene expression, being present in all cellular organisms. Transcriptional activation of heat shock genes by increased temperature or other cellular stresses is mediated by the binding of a heat shock factor (HSF) to a conserved nucleotide sequence (the heat shock element) present in the promoter of heat-inducible genes. Despite the high degree of conservation of this response, embryonic stages of development are characterized by the absence of a heat shock response. Murine erythroleukemia (MEL) cells also lack this response, and we report here a detailed characterization of this defect for one of the most highly conserved of these genes, hsp70. Surprisingly, heat-induced transcriptional activation of this gene does not occur, despite the induction of a protein with the binding specificity of murine HSF. However, the MEL HSF differs slightly in apparent size from the HSF in 3T3 cells, which exhibit a normal heat shock response. These data suggest that activation of mammalian HSF by heat requires at least two separate steps: an alteration of binding activity followed by further modification that activates transcription. MEL cells do not respond to heat shock because they lack the ability to perform this secondary modification. These cells provide a useful system for characterizing heat stock activation in mammals.