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

Fingerprint

Cytomegalovirus
Endoplasmic Reticulum
Transcriptional Activation
Endoplasmic Reticulum Stress
Response Elements
Chromatin
TATA-Binding Protein Associated Factors
TATA-Box Binding Protein
Histone Acetyltransferases
Gene Expression
Leucine Zippers
Zinc Fingers
Virus Diseases
Growth
Histones
Proteins
Adenosine Triphosphate
Binding Sites
glucose-regulated proteins
cytomegalovirus IE1 protein

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

Cite this

Transcriptional activation of endoplasmic reticulum chaperone GRP78 by HCMV IE1-72 protein. / Shi-Chen Ou, D.; Lee, Sung-Bau; Chu, Chi-Shuen; Chang, Liang-Hao; Chung, Bon-Chu; Juan, Li-Jung.

In: Cell Research, Vol. 21, No. 4, 2011, p. 642-653.

Research output: Contribution to journalArticle

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, vol. 21, no. 4, pp. 642-653. https://doi.org/10.1038/cr.2011.10
Shi-Chen Ou, D. ; Lee, Sung-Bau ; Chu, Chi-Shuen ; Chang, Liang-Hao ; Chung, Bon-Chu ; Juan, Li-Jung. / Transcriptional activation of endoplasmic reticulum chaperone GRP78 by HCMV IE1-72 protein. In: Cell Research. 2011 ; Vol. 21, No. 4. pp. 642-653.
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title = "Transcriptional activation of endoplasmic reticulum chaperone GRP78 by HCMV IE1-72 protein",
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. {\circledC} 2011 IBCB, SIBS, CAS All rights reserved.",
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, ER stress elements, GRP78, HCMV, IE1-72, TAF1",
author = "{Shi-Chen Ou}, D. and Sung-Bau Lee and Chi-Shuen Chu and Liang-Hao Chang and Bon-Chu Chung and Li-Jung Juan",
note = "被引用次數:9 Export Date: 28 March 2016 通訊地址: Chung, B.-C.; Institute of Molecular and Cellular Biology, National Tsing Hua University, 101, Kuang-Fu Road, Hsinchu 300, Taiwan; 電子郵件: mbchung@sinica.edu.tw 化學物質/CAS: histone, 9062-68-4; CCAAT-Binding Factor; Heat-Shock Proteins; Histones; IE1 protein, cytomegalovirus; Immediate-Early Proteins; Molecular Chaperones; TATA-Binding Protein Associated Factors; molecular chaperone GRP78 參考文獻: Lee, A.S., The glucose-regulated proteins: Stress induction and clinical applications (2001) Trends in Biochemical Sciences, 26 (8), pp. 504-510. , DOI 10.1016/S0968-0004(01)01908-9, PII S0968000401019089; Fink, A.L., Chaperone-mediated protein folding (1999) Physiological Reviews, 79 (2), pp. 425-449; Bertolotti, A., Zhang, Y., Hendershot, L.M., Harding, H.P., Ron, D., Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response (2000) Nat Cell Biol, 2, pp. 326-332; Okada, T., Yoshida, H., Akazawa, R., Negishi, M., Mori, K., Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response (2002) Biochemical Journal, 366 (2), pp. 585-594. , DOI 10.1042/BJ20020391; Shen, J., Chen, X., Hendershot, L., Prywes, R., ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of golgi localization signals (2002) Developmental Cell, 3 (1), pp. 99-111. , DOI 10.1016/S1534-5807(02)00203-4; Harding, H.P., Zhang, Y., Ron, D., Protein translation and folding are coupled by an endoplasmic- Reticulum-resident kinase (1999) Nature, 397 (6716), pp. 271-274. , DOI 10.1038/16729; Yoshida, H., Matsui, T., Yamamoto, A., Okada, T., Mori, K., XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor (2001) Cell, 107 (7), pp. 881-891. , DOI 10.1016/S0092-8674(01)00611-0; Mori, K., Signaling pathways in the unfolded protein response: Development from yeast to mammals (2009) J Biochem, 146, pp. 743-750; Li, M., Baumeister, P., Roy, B., Phan, T., Foti, D., Luo, S., Lee, A.S., ATF6 as a transcription activator of the endoplasmic reticulum stress element: Thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1 (2000) Molecular and Cellular Biology, 20 (14), pp. 5096-5106. , DOI 10.1128/MCB.20.14.5096-5106.2000; Yoshida, H., Haze, K., Yanagi, H., Yura, T., Mori, K., Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins. Involvement of basic leucine zipper transcription factors (1998) J Biol Chem, 273, pp. 33741-33749; Roy, B., Li, W.W., Lee, A.S., Calcium-sensitive transcriptional activation of the proximal CCAAT regulatory element of the grp78/BiP promoter by the human nuclear factor CBF/NF-Y (1996) Journal of Biological Chemistry, 271 (46), pp. 28995-29002. , DOI 10.1074/jbc.271.46.28995; Abdelrahim, M., Liu, S., Safe, S., Induction of endoplasmic reticulum-induced stress genes in Panc-1 pancreatic cancer cells is dependent on Sp proteins (2005) Journal of Biological Chemistry, 280 (16), pp. 16508-16513. , DOI 10.1074/jbc.C500030200; Parker, R., Phan, T., Baumeister, P., Roy, B., Cheriyath, V., Roy, A.L., Lee, A.S., Identification of TFII-I as the endoplasmic reticulum stress response element binding factor ERSF: Its autoregulation by stress and interaction with ATF6 (2001) Molecular and Cellular Biology, 21 (9), pp. 3220-3233. , DOI 10.1128/MCB.21.9.3220-3233.2001; Mayer, M.P., Recruitment of Hsp70 chaperones: A crucial part of viral survival strategies (2005) Reviews of Physiology, Biochemistry and Pharmacology, 153, pp. 1-46. , DOI 10.1007/s10254-004-0025-5; Tardif, K.D., Waris, G., Siddiqui, A., Hepatitis C virus, ER stress, and oxidative stress (2005) Trends Microbiol, 13, pp. 159-163; Buchkovich, N.J., Maguire, T.G., Paton, A.W., Paton, J.C., Alwine, J.C., The endoplasmic reticulum chaperone BiP/GRP78 is important in the structure and function of the HCMV assembly compartment (2009) J Virol, 83, pp. 11421-11428; Isler, J.A., Skalet, A.H., Alwine, J.C., Human cytomegalovirus infection activates and regulates the unfolded protein response (2005) Journal of Virology, 79 (11), pp. 6890-6899. , DOI 10.1128/JVI.79.11.6890-6899.2005; Landolfo, S., Gariglio, M., Gribaudo, G., Lembo, D., The human cytomegalovirus (2003) Pharmacology and Therapeutics, 98 (3), pp. 269-297. , DOI 10.1016/S0163-7258(03)00034-2; Mocaski, E.S., Shenk, T., Pass, R.F., Cytomegalovirus: Replication (2007) Fields Virology, pp. 2718-2727. , Knipe DM, Howley PM, eds. 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language = "English",
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pages = "642--653",
journal = "Cell Research",
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TY - JOUR

T1 - Transcriptional activation of endoplasmic reticulum chaperone GRP78 by HCMV IE1-72 protein

AU - Shi-Chen Ou, D.

AU - Lee, Sung-Bau

AU - Chu, Chi-Shuen

AU - Chang, Liang-Hao

AU - Chung, Bon-Chu

AU - Juan, Li-Jung

N1 - 被引用次數:9 Export Date: 28 March 2016 通訊地址: Chung, B.-C.; Institute of Molecular and Cellular Biology, National Tsing Hua University, 101, Kuang-Fu Road, Hsinchu 300, Taiwan; 電子郵件: mbchung@sinica.edu.tw 化學物質/CAS: histone, 9062-68-4; CCAAT-Binding Factor; Heat-Shock Proteins; Histones; IE1 protein, cytomegalovirus; Immediate-Early Proteins; Molecular Chaperones; TATA-Binding Protein Associated Factors; molecular chaperone GRP78 參考文獻: Lee, A.S., The glucose-regulated proteins: Stress induction and clinical applications (2001) Trends in Biochemical Sciences, 26 (8), pp. 504-510. , DOI 10.1016/S0968-0004(01)01908-9, PII S0968000401019089; Fink, A.L., Chaperone-mediated protein folding (1999) Physiological Reviews, 79 (2), pp. 425-449; Bertolotti, A., Zhang, Y., Hendershot, L.M., Harding, H.P., Ron, D., Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response (2000) Nat Cell Biol, 2, pp. 326-332; Okada, T., Yoshida, H., Akazawa, R., Negishi, M., Mori, K., Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response (2002) Biochemical Journal, 366 (2), pp. 585-594. , DOI 10.1042/BJ20020391; Shen, J., Chen, X., Hendershot, L., Prywes, R., ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of golgi localization signals (2002) Developmental Cell, 3 (1), pp. 99-111. , DOI 10.1016/S1534-5807(02)00203-4; Harding, H.P., Zhang, Y., Ron, D., Protein translation and folding are coupled by an endoplasmic- Reticulum-resident kinase (1999) Nature, 397 (6716), pp. 271-274. , DOI 10.1038/16729; Yoshida, H., Matsui, T., Yamamoto, A., Okada, T., Mori, K., XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor (2001) Cell, 107 (7), pp. 881-891. , DOI 10.1016/S0092-8674(01)00611-0; Mori, K., Signaling pathways in the unfolded protein response: Development from yeast to mammals (2009) J Biochem, 146, pp. 743-750; Li, M., Baumeister, P., Roy, B., Phan, T., Foti, D., Luo, S., Lee, A.S., ATF6 as a transcription activator of the endoplasmic reticulum stress element: Thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1 (2000) Molecular and Cellular Biology, 20 (14), pp. 5096-5106. , DOI 10.1128/MCB.20.14.5096-5106.2000; Yoshida, H., Haze, K., Yanagi, H., Yura, T., Mori, K., Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins. Involvement of basic leucine zipper transcription factors (1998) J Biol Chem, 273, pp. 33741-33749; Roy, B., Li, W.W., Lee, A.S., Calcium-sensitive transcriptional activation of the proximal CCAAT regulatory element of the grp78/BiP promoter by the human nuclear factor CBF/NF-Y (1996) Journal of Biological Chemistry, 271 (46), pp. 28995-29002. , DOI 10.1074/jbc.271.46.28995; Abdelrahim, M., Liu, S., Safe, S., Induction of endoplasmic reticulum-induced stress genes in Panc-1 pancreatic cancer cells is dependent on Sp proteins (2005) Journal of Biological Chemistry, 280 (16), pp. 16508-16513. , DOI 10.1074/jbc.C500030200; Parker, R., Phan, T., Baumeister, P., Roy, B., Cheriyath, V., Roy, A.L., Lee, A.S., Identification of TFII-I as the endoplasmic reticulum stress response element binding factor ERSF: Its autoregulation by stress and interaction with ATF6 (2001) Molecular and Cellular Biology, 21 (9), pp. 3220-3233. , DOI 10.1128/MCB.21.9.3220-3233.2001; Mayer, M.P., Recruitment of Hsp70 chaperones: A crucial part of viral survival strategies (2005) Reviews of Physiology, Biochemistry and Pharmacology, 153, pp. 1-46. , DOI 10.1007/s10254-004-0025-5; Tardif, K.D., Waris, G., Siddiqui, A., Hepatitis C virus, ER stress, and oxidative stress (2005) Trends Microbiol, 13, pp. 159-163; Buchkovich, N.J., Maguire, T.G., Paton, A.W., Paton, J.C., Alwine, J.C., The endoplasmic reticulum chaperone BiP/GRP78 is important in the structure and function of the HCMV assembly compartment (2009) J Virol, 83, pp. 11421-11428; Isler, J.A., Skalet, A.H., Alwine, J.C., Human cytomegalovirus infection activates and regulates the unfolded protein response (2005) Journal of Virology, 79 (11), pp. 6890-6899. , DOI 10.1128/JVI.79.11.6890-6899.2005; Landolfo, S., Gariglio, M., Gribaudo, G., Lembo, D., The human cytomegalovirus (2003) Pharmacology and Therapeutics, 98 (3), pp. 269-297. , DOI 10.1016/S0163-7258(03)00034-2; Mocaski, E.S., Shenk, T., Pass, R.F., Cytomegalovirus: Replication (2007) Fields Virology, pp. 2718-2727. , Knipe DM, Howley PM, eds. 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PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - ER stress elements

KW - GRP78

KW - HCMV

KW - IE1-72

KW - TAF1

KW - CCAAT binding factor

KW - chaperone

KW - heat shock protein

KW - histone

KW - IE1 protein, cytomegalovirus

KW - immediate early protein

KW - molecular chaperone GRP78

KW - TATA binding protein associated factor

KW - article

KW - cell line

KW - chromatin immunoprecipitation

KW - Cytomegalovirus

KW - endoplasmic reticulum

KW - gene expression

KW - genetics

KW - human

KW - metabolism

KW - polymerase chain reaction

KW - promoter region

KW - transcription initiation

KW - Western blotting

KW - Blotting, Western

KW - CCAAT-Binding Factor

KW - Cell Line

KW - Chromatin Immunoprecipitation

KW - Endoplasmic Reticulum

KW - Gene Expression

KW - Heat-Shock Proteins

KW - Histones

KW - Humans

KW - Immediate-Early Proteins

KW - Molecular Chaperones

KW - Polymerase Chain Reaction

KW - Promoter Regions, Genetic

KW - TATA-Binding Protein Associated Factors

KW - Transcriptional Activation

KW - Human herpesvirus 5

KW - ER stress elements

KW - GRP78

KW - HCMV

KW - IE1-72

KW - TAF1

U2 - 10.1038/cr.2011.10

DO - 10.1038/cr.2011.10

M3 - Article

VL - 21

SP - 642

EP - 653

JO - Cell Research

JF - Cell Research

SN - 1001-0602

IS - 4

ER -