Transcriptional activation of endoplasmic reticulum chaperone GRP78 by HCMV IE1-72 protein

D. Shi-Chen Ou, Sung-Bau Lee, Chi-Shuen Chu, Liang-Hao Chang, Bon-Chu Chung, Li-Jung Juan

研究成果: 雜誌貢獻文章同行評審

17 引文 斯高帕斯(Scopus)

摘要

Glucose-regulated protein 78 (GRP78), a key regulator of endoplasmic reticulum (ER) stress, facilitates cancer cell growth and viral replication. The mechanism leading to grp78 gene activation during viral infection is largely unknown. In this study, we show that the immediate-early 1 (IE1-72) protein of the human cytomegalovirus (HCMV) is essential for HCMV-mediated GRP78 activation. IE1-72 upregulated grp78 gene expression depending on the ATP-binding site, the zinc-finger domain and the putative leucine-zipper motif of IE1-72, as well as the ER stress response elements (ERSEs) on the grp78 promoter. The purified IE1-72 protein bound to the CCAAT box within ERSE in vitro, whereas deletion mutants of IE1-72 deficient in grp78 promoter stimulation failed to do so. Moreover, IE1-72 binding to the grp78 promoter in infected cells accompanied the recruitment of TATA box-binding protein-associated factor 1 (TAF1), a histone acetyltransferase, and the increased level of acetylated histone H4, an indicator of active-state chromatin. These results provide evidence that HCMV IE1-72 activates grp78 gene expression through direct promoter binding and modulation of the local chromatin structure, indicating an active viral mechanism of cellular chaperone induction for viral growth. © 2011 IBCB, SIBS, CAS All rights reserved.
原文英語
頁(從 - 到)642-653
頁數12
期刊Cell Research
21
發行號4
DOIs
出版狀態已發佈 - 2011

Keywords

  • ER stress elements
  • GRP78
  • HCMV
  • IE1-72
  • TAF1

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