Regulation of Egr-1 by association with the proteasome component C8
Regulation of Egr-1 by association with the proteasome component C8
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DOI：
10.1016/s0167-4889(02)00310-5
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发表时间：
2002-10-21
影响因子：
5.1
通讯作者：
Kim, KW
中科院分区：
文献类型：
--
作者：
Bae, MH;Jeong, CH;Kim, KW
主要应答转录因子Egr-1被多种细胞外刺激迅速激活。Egr-1的激活被证明是缺血激活的主开关，可以触发炎症、凝血和血管高通透性的关键调节因子的表达。Egr-1是一种短寿命蛋白，但调控其稳定性的机制尚未明确。本研究通过酵母双杂交筛选发现，Egr-1与PRC8（蛋白酶体组分C8）相互作用显著，并通过GST下拉实验和共免疫沉淀证实了其特异性相互作用。有趣的是，我们发现PRC8介导的Egr-1活性调节与蛋白酶体途径相关，PRC8抑制Egr-1的转录活性。此外，Egr-1蛋白被泛素特异性多泛素化。这些数据强烈暗示Egr-1蛋白是泛素依赖性蛋白酶体途径蛋白水解的靶标。(C) 2002 Elsevier Science B.V.版权所有
Primary response transcription factor, Egr-1, is rapidly activated by a variety of extracellular stimuli. Activation of Egr-1 is shown to function as a master switch activated by ischemia to trigger expression of pivotal regulators of inflammation, coagulation and vascular hyperpermeability. Egr-1 is a short-lived protein, but the mechanism that regulates its stability has not yet been clarified. In this study, the yeast two-hybrid screening revealed that Egr-1 interacts significantly with PRC8 (proteasome component C8) and the specific interaction was confirmed by GST pull-down assay and coimmunoprecipitation. Interestingly, we found that the PRC8-mediated regulation of Egr-1 activity is associated with the proteasome pathway and PRC8 inhibits the transcriptional activity of Egr-1. In addition, Egr-1 protein was specifically multiubiquitinated by ubiquitin. These data strongly imply that Egr-1 protein is targeted for proteolysis by the ubiquitin-dependent proteasome pathway. (C) 2002 Elsevier Science B.V. All rights reserved.