SREBP-1a activation by HBx and the effect on hepatitis B virus enhancer II/core promoter

Autores
Qiao, Ling; Wu, Qi; Lu, Xinya; Zhou, Yan; Fernández Alvarez, Ana Julia; Ye, Lihong; Zhang, Xiaodong; Han, Jihong; Casado, Marta; Liu, Quiang
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hepatitis B virus (HBV) X protein (HBx) plays an important role in HBV pathogenesis by regulating gene expression. Sterol regulatory element binding protein-1a (SREBP-1a) is a key transcriptional factor for modulating fatty acid and cholesterol synthesis. Here we demonstrated that HBx increased mature SREBP-1a protein level in the nucleus and its activity as a transcription factor. We further showed that the up-regulation of SREBP-1a by HBx occurred at the transcriptional level after ectopic expression and in the context of HBV replication. Deletional analysis using SREBP-1a promoter revealed that the sequence from -436 to -398 in the promoter was required for its activation by HBx. This promoter region possesses the binding sequences for two basic leucine zipper (b-ZIP) transcription factors, namely C/EBP and E4BP4. Mutagenesis of the binding sequences on the SREBP-1a promoter and ectopic expression experiments demonstrated that C/EBPα enhanced SREBP-1a activation by HBx, while E4BP4 had an inhibitory effect. C/EBPα was able to significantly reverse the inhibitory activity of E4BP4 on SREBP-1a promoter. These results demonstrated that HBx activates SREBP-1a activity at the transcription level through a complex mechanism involving two bZIP transcription factors C/EBP and E4BP4 with C/EBP being the dominant positive factor. Finally, we showed that knocking down SREBP-1 abolishes HBV enhancer II/core promoter activation by HBx.
Fil: Qiao, Ling. University Of Saskatchewan; Canadá
Fil: Wu, Qi. University Of Saskatchewan; Canadá
Fil: Lu, Xinya. University Of Saskatchewan; Canadá
Fil: Zhou, Yan. University Of Saskatchewan; Canadá
Fil: Fernández Alvarez, Ana Julia. Consejo Superior de Investigaciones Cientificas; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Ye, Lihong. Nankai University; China
Fil: Zhang, Xiaodong. Nankai University; China
Fil: Han, Jihong. Nankai University; China
Fil: Casado, Marta. Consejo Superior de Investigaciones Cientificas; España
Fil: Liu, Quiang. University Of Saskatchewan; Canadá
Materia
Transcription
Hepatitis
Promoter
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/20180
Acceder
id CONICETDig_fcfb3f158b959757cb6cebb962a70a76
oai_identifier_str oai:ri.conicet.gov.ar:11336/20180
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling SREBP-1a activation by HBx and the effect on hepatitis B virus enhancer II/core promoterQiao, LingWu, QiLu, XinyaZhou, YanFernández Alvarez, Ana JuliaYe, LihongZhang, XiaodongHan, JihongCasado, MartaLiu, QuiangTranscriptionHepatitisPromoterhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Hepatitis B virus (HBV) X protein (HBx) plays an important role in HBV pathogenesis by regulating gene expression. Sterol regulatory element binding protein-1a (SREBP-1a) is a key transcriptional factor for modulating fatty acid and cholesterol synthesis. Here we demonstrated that HBx increased mature SREBP-1a protein level in the nucleus and its activity as a transcription factor. We further showed that the up-regulation of SREBP-1a by HBx occurred at the transcriptional level after ectopic expression and in the context of HBV replication. Deletional analysis using SREBP-1a promoter revealed that the sequence from -436 to -398 in the promoter was required for its activation by HBx. This promoter region possesses the binding sequences for two basic leucine zipper (b-ZIP) transcription factors, namely C/EBP and E4BP4. Mutagenesis of the binding sequences on the SREBP-1a promoter and ectopic expression experiments demonstrated that C/EBPα enhanced SREBP-1a activation by HBx, while E4BP4 had an inhibitory effect. C/EBPα was able to significantly reverse the inhibitory activity of E4BP4 on SREBP-1a promoter. These results demonstrated that HBx activates SREBP-1a activity at the transcription level through a complex mechanism involving two bZIP transcription factors C/EBP and E4BP4 with C/EBP being the dominant positive factor. Finally, we showed that knocking down SREBP-1 abolishes HBV enhancer II/core promoter activation by HBx.Fil: Qiao, Ling. University Of Saskatchewan; CanadáFil: Wu, Qi. University Of Saskatchewan; CanadáFil: Lu, Xinya. University Of Saskatchewan; CanadáFil: Zhou, Yan. University Of Saskatchewan; CanadáFil: Fernández Alvarez, Ana Julia. Consejo Superior de Investigaciones Cientificas; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ye, Lihong. Nankai University; ChinaFil: Zhang, Xiaodong. Nankai University; ChinaFil: Han, Jihong. Nankai University; ChinaFil: Casado, Marta. Consejo Superior de Investigaciones Cientificas; EspañaFil: Liu, Quiang. University Of Saskatchewan; CanadáAcademic Press2013-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/20180Qiao, Ling; Wu, Qi; Lu, Xinya; Zhou, Yan; Fernández Alvarez, Ana Julia; et al.; SREBP-1a activation by HBx and the effect on hepatitis B virus enhancer II/core promoter; Academic Press; Biochemical And Biophysical Research Communications; 432; 4; 3-2013; 643-6490006-291X1090-2104CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0006291X13002775info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbrc.2013.02.030info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:06:32Zoai:ri.conicet.gov.ar:11336/20180instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:06:33.078CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv SREBP-1a activation by HBx and the effect on hepatitis B virus enhancer II/core promoter
title SREBP-1a activation by HBx and the effect on hepatitis B virus enhancer II/core promoter
spellingShingle SREBP-1a activation by HBx and the effect on hepatitis B virus enhancer II/core promoter
Qiao, Ling
Transcription
Hepatitis
Promoter
title_short SREBP-1a activation by HBx and the effect on hepatitis B virus enhancer II/core promoter
title_full SREBP-1a activation by HBx and the effect on hepatitis B virus enhancer II/core promoter
title_fullStr SREBP-1a activation by HBx and the effect on hepatitis B virus enhancer II/core promoter
title_full_unstemmed SREBP-1a activation by HBx and the effect on hepatitis B virus enhancer II/core promoter
title_sort SREBP-1a activation by HBx and the effect on hepatitis B virus enhancer II/core promoter
dc.creator.none.fl_str_mv Qiao, Ling
Wu, Qi
Lu, Xinya
Zhou, Yan
Fernández Alvarez, Ana Julia
Ye, Lihong
Zhang, Xiaodong
Han, Jihong
Casado, Marta
Liu, Quiang
author Qiao, Ling
author_facet Qiao, Ling
Wu, Qi
Lu, Xinya
Zhou, Yan
Fernández Alvarez, Ana Julia
Ye, Lihong
Zhang, Xiaodong
Han, Jihong
Casado, Marta
Liu, Quiang
author_role author
author2 Wu, Qi
Lu, Xinya
Zhou, Yan
Fernández Alvarez, Ana Julia
Ye, Lihong
Zhang, Xiaodong
Han, Jihong
Casado, Marta
Liu, Quiang
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Transcription
Hepatitis
Promoter
topic Transcription
Hepatitis
Promoter
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Hepatitis B virus (HBV) X protein (HBx) plays an important role in HBV pathogenesis by regulating gene expression. Sterol regulatory element binding protein-1a (SREBP-1a) is a key transcriptional factor for modulating fatty acid and cholesterol synthesis. Here we demonstrated that HBx increased mature SREBP-1a protein level in the nucleus and its activity as a transcription factor. We further showed that the up-regulation of SREBP-1a by HBx occurred at the transcriptional level after ectopic expression and in the context of HBV replication. Deletional analysis using SREBP-1a promoter revealed that the sequence from -436 to -398 in the promoter was required for its activation by HBx. This promoter region possesses the binding sequences for two basic leucine zipper (b-ZIP) transcription factors, namely C/EBP and E4BP4. Mutagenesis of the binding sequences on the SREBP-1a promoter and ectopic expression experiments demonstrated that C/EBPα enhanced SREBP-1a activation by HBx, while E4BP4 had an inhibitory effect. C/EBPα was able to significantly reverse the inhibitory activity of E4BP4 on SREBP-1a promoter. These results demonstrated that HBx activates SREBP-1a activity at the transcription level through a complex mechanism involving two bZIP transcription factors C/EBP and E4BP4 with C/EBP being the dominant positive factor. Finally, we showed that knocking down SREBP-1 abolishes HBV enhancer II/core promoter activation by HBx.
Fil: Qiao, Ling. University Of Saskatchewan; Canadá
Fil: Wu, Qi. University Of Saskatchewan; Canadá
Fil: Lu, Xinya. University Of Saskatchewan; Canadá
Fil: Zhou, Yan. University Of Saskatchewan; Canadá
Fil: Fernández Alvarez, Ana Julia. Consejo Superior de Investigaciones Cientificas; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Ye, Lihong. Nankai University; China
Fil: Zhang, Xiaodong. Nankai University; China
Fil: Han, Jihong. Nankai University; China
Fil: Casado, Marta. Consejo Superior de Investigaciones Cientificas; España
Fil: Liu, Quiang. University Of Saskatchewan; Canadá
description Hepatitis B virus (HBV) X protein (HBx) plays an important role in HBV pathogenesis by regulating gene expression. Sterol regulatory element binding protein-1a (SREBP-1a) is a key transcriptional factor for modulating fatty acid and cholesterol synthesis. Here we demonstrated that HBx increased mature SREBP-1a protein level in the nucleus and its activity as a transcription factor. We further showed that the up-regulation of SREBP-1a by HBx occurred at the transcriptional level after ectopic expression and in the context of HBV replication. Deletional analysis using SREBP-1a promoter revealed that the sequence from -436 to -398 in the promoter was required for its activation by HBx. This promoter region possesses the binding sequences for two basic leucine zipper (b-ZIP) transcription factors, namely C/EBP and E4BP4. Mutagenesis of the binding sequences on the SREBP-1a promoter and ectopic expression experiments demonstrated that C/EBPα enhanced SREBP-1a activation by HBx, while E4BP4 had an inhibitory effect. C/EBPα was able to significantly reverse the inhibitory activity of E4BP4 on SREBP-1a promoter. These results demonstrated that HBx activates SREBP-1a activity at the transcription level through a complex mechanism involving two bZIP transcription factors C/EBP and E4BP4 with C/EBP being the dominant positive factor. Finally, we showed that knocking down SREBP-1 abolishes HBV enhancer II/core promoter activation by HBx.
publishDate 2013
dc.date.none.fl_str_mv 2013-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/20180
Qiao, Ling; Wu, Qi; Lu, Xinya; Zhou, Yan; Fernández Alvarez, Ana Julia; et al.; SREBP-1a activation by HBx and the effect on hepatitis B virus enhancer II/core promoter; Academic Press; Biochemical And Biophysical Research Communications; 432; 4; 3-2013; 643-649
0006-291X
1090-2104
CONICET Digital
CONICET
url http://hdl.handle.net/11336/20180
identifier_str_mv Qiao, Ling; Wu, Qi; Lu, Xinya; Zhou, Yan; Fernández Alvarez, Ana Julia; et al.; SREBP-1a activation by HBx and the effect on hepatitis B virus enhancer II/core promoter; Academic Press; Biochemical And Biophysical Research Communications; 432; 4; 3-2013; 643-649
0006-291X
1090-2104
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0006291X13002775
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbrc.2013.02.030
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press
publisher.none.fl_str_mv Academic Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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