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

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. © 2011 IBCB, SIBS, CAS All rights reserved.
Original languageEnglish
Pages (from-to)642-653
Number of pages12
JournalCell Research
Volume21
Issue number4
DOIs
Publication statusPublished - 2011

Keywords

  • ER stress elements
  • GRP78
  • HCMV
  • IE1-72
  • TAF1
  • CCAAT binding factor
  • chaperone
  • heat shock protein
  • histone
  • IE1 protein, cytomegalovirus
  • immediate early protein
  • molecular chaperone GRP78
  • TATA binding protein associated factor
  • article
  • cell line
  • chromatin immunoprecipitation
  • Cytomegalovirus
  • endoplasmic reticulum
  • gene expression
  • genetics
  • human
  • metabolism
  • polymerase chain reaction
  • promoter region
  • transcription initiation
  • Western blotting
  • Blotting, Western
  • CCAAT-Binding Factor
  • Cell Line
  • Chromatin Immunoprecipitation
  • Endoplasmic Reticulum
  • Gene Expression
  • Heat-Shock Proteins
  • Histones
  • Humans
  • Immediate-Early Proteins
  • Molecular Chaperones
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • TATA-Binding Protein Associated Factors
  • Transcriptional Activation
  • Human herpesvirus 5

Fingerprint Dive into the research topics of 'Transcriptional activation of endoplasmic reticulum chaperone GRP78 by HCMV IE1-72 protein'. Together they form a unique fingerprint.

  • Cite this