Mathur S K, Sistonen L, Brown I R, Murphy S P, Sarge K D, Morimoto R I
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208.
Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8695-9. doi: 10.1073/pnas.91.18.8695.
One of the basic features of the inducible heat shock response is the activation of heat shock factor which results in the rapid transcriptional induction of the heat shock genes. Although it is widely considered that the heat shock response is ubiquitous, several reports have indicated that the transcriptional response can vary in both intensity and kinetics and often in a tissue-specific manner. Of interest have been studies on the expression of heat shock genes in the brain, particularly observations that certain cultured neuronal cells exhibit a diminished heat shock response. We demonstrate that transcription of the gene encoding a 70-kDa heat shock protein (hsp70) is diminished upon heat shock in Y79 human retinoblastoma cells (which are of neuronal origin) despite both the activation of heat shock factor 1 and induced transcription of another heat shock gene, hsp90 alpha. This uncoupling of stress-induced transcription of the hsp70 and hsp90 alpha genes, which are typically coordinately regulated in response to stress, appears to be due to the selective inability of trans-acting factors, including heat shock factor 1, to bind in vivo to the hsp70 promoter as the result of a chromatin-mediated effect.
诱导性热休克反应的基本特征之一是热休克因子的激活，这会导致热休克基因的快速转录诱导。尽管人们普遍认为热休克反应是普遍存在的，但有几份报告表明，转录反应在强度和动力学方面都可能有所不同，而且往往具有组织特异性。对大脑中热休克基因表达的研究很有意思，特别是某些培养的神经元细胞表现出热休克反应减弱的观察结果。我们证明，在Y79人视网膜母细胞瘤细胞（源自神经元）中，热休克后编码70 kDa热休克蛋白（hsp70）的基因转录减少，尽管热休克因子1被激活且另一个热休克基因hsp90α的转录也被诱导。热休克蛋白70和热休克蛋白90α基因的应激诱导转录通常在应激反应中受到协调调节，但这种解偶联现象似乎是由于包括热休克因子1在内的反式作用因子因染色质介导的效应而在体内无法与热休克蛋白70启动子结合所致。
