Head M W, Hurwitz L, Goldman J E
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
J Cell Sci. 1996 May;109 ( Pt 5):1029-39. doi: 10.1242/jcs.109.5.1029.
The coordinated cellular responses to physiological stress are known to be effected in part by the activation of heat-shock factor 1, a transcriptional activator protein capable of binding to, and inducing transcription from genes containing heat shock elements. Other stress responsive signal transduction pathways also exist including the stress activated protein kinase cascade that regulates the activity of the transcription factor AP1. We have examined the expression of the low molecular stress proteins, heat shock protein 27 and alpha B-crystallin in astrocytes in response to physiological stress of different types and asked what component of this induction is effected at the transcriptional level and whether activation of heat shock factor 1 and AP1 might account for these events. We have found that stress regulated induction of alpha B-crystallin has a strong transcriptional component and that it may be effected by at least two different transcriptional mechanisms. In one set of phenomena, represented here by cadmium exposure, alpha B-crystallin and heat shock protein 27 are coordinately regulated and this occurs in the presence of activated heat shock factor 1. In the second series of phenomena, represented here by hypertonic stress, alpha B-crystallin is induced in the absence of heat shock factor activation and in the absence of any corresponding change in heat shock protein 27 expression. Although hypertonic stress does activate an AP1-like binding activity, the AP1 consensus binding site in the alpha B-crystallin promoter does not appear to be a target for this hypertonic stress inducible activity. These data suggest that the hypertonic stress response is effected through a heat shock factor independent mechanism and that hypertonic stress regulated induction of alpha B-crystallin does not directly depend on the SAPK pathway and AP1 activity.
已知细胞对生理应激的协同反应部分是由热休克因子1的激活所介导的，热休克因子1是一种转录激活蛋白，能够结合含有热休克元件的基因并诱导其转录。还存在其他应激反应信号转导途径，包括调节转录因子AP1活性的应激激活蛋白激酶级联反应。我们研究了不同类型生理应激下星形胶质细胞中低分子量应激蛋白热休克蛋白27和αB晶状体蛋白的表达，并探讨了这种诱导作用在转录水平上是由什么成分介导的，以及热休克因子1和AP1的激活是否可以解释这些现象。我们发现，应激调节的αB晶状体蛋白诱导具有很强的转录成分，并且可能由至少两种不同的转录机制介导。在一组现象中，以镉暴露为例，αB晶状体蛋白和热休克蛋白27受到协同调节，且这种调节发生在热休克因子1被激活的情况下。在第二组现象中，以高渗应激为例，αB晶状体蛋白在热休克因子未激活且热休克蛋白27表达没有任何相应变化的情况下被诱导。尽管高渗应激确实激活了一种类似AP1的结合活性，但αB晶状体蛋白启动子中的AP1共有结合位点似乎不是这种高渗应激诱导活性的作用靶点。这些数据表明，高渗应激反应是通过一种不依赖热休克因子的机制介导的，并且高渗应激调节的αB晶状体蛋白诱导并不直接依赖于SAPK途径和AP1活性。
