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

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

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)642-653
Number of pages12
JournalCell Research
Volume21
Issue number4
DOIs
Publication statusPublished - Apr 1 2011

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Shi-Chen Ou, D., Lee, S. B., Chu, C. S., Chang, L. H., Chung, B. C., & Juan, L. J. (2011). Transcriptional activation of endoplasmic reticulum chaperone GRP78 by HCMV IE1-72 protein. Cell Research, 21(4), 642-653. https://doi.org/10.1038/cr.2011.10