Cotto J J, Kline M, Morimoto R I
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
J Biol Chem. 1996 Feb 16;271(7):3355-8. doi: 10.1074/jbc.271.7.3355.
Exposure of mammalian cells in culture to the anti-inflammatory drugs sodium salicylate or indomethacin results in activation of heat shock factor 1 (HSF1) DNA binding activity. We have previously shown that the drug-induced HSF1 becomes associated with the heat shock elements of the hsp70 promoter, yet transcription of the hsp70 gene is not induced (Jurivich, D. A., Sistonen, L., Kroes, R. A., and Morimoto, R. I. (1992) Science 255, 1243-1245). In this study, we have examined the basis for uncoupling the heat shock transcriptional response. Comparison of heat shock and drug-induced forms of HSF1 has revealed that the transcriptionally inert drug-induced HSF1 is constitutively but not inducibly serine-phosphorylated, whereas heat shock-induced HSF1 is both constitutively and inducibly serine-phosphorylated. The transcriptionally inert intermediate represented by drug-induced HSF1 can be converted to the transcriptionally active state by a subsequent exposure to heat shock. The only detectable change in HSF1 is the acquisition of inducible serine phosphorylation. These data reveal that acquisition of the trimeric DNA binding state of HSF1 is independent of and precedes inducible phosphorylation and furthermore that inducible phosphorylation correlates with transcriptional activation.
在培养过程中，将哺乳动物细胞暴露于抗炎药物水杨酸钠或吲哚美辛会导致热休克因子1（HSF1）的DNA结合活性激活。我们之前已经表明，药物诱导的HSF1与hsp70启动子的热休克元件相关联，但hsp70基因的转录并未被诱导（Jurivich，D.A.，Sistonen，L.，Kroes，R.A.，和Morimoto，R.I.（1992）《科学》255，1243 - 1245）。在本研究中，我们研究了热休克转录反应解偶联的基础。对热休克诱导型和药物诱导型HSF1的比较表明，转录无活性的药物诱导型HSF1组成性地而非诱导性地被丝氨酸磷酸化，而热休克诱导型HSF1则组成性地和诱导性地都被丝氨酸磷酸化。由药物诱导型HSF1代表的转录无活性中间体可通过随后暴露于热休克而转化为转录活性状态。HSF1中唯一可检测到的变化是获得了诱导性丝氨酸磷酸化。这些数据表明，HSF1三聚体DNA结合状态的获得独立于诱导性磷酸化且先于诱导性磷酸化，此外，诱导性磷酸化与转录激活相关。
