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Article: Early Activation of the Kaposi's Sarcoma-Associated Herpesvirus RTA, RAP, and MTA Promoters by the Tetradecanoyl Phorbol Acetate-Induced AP1 Pathway

TitleEarly Activation of the Kaposi's Sarcoma-Associated Herpesvirus RTA, RAP, and MTA Promoters by the Tetradecanoyl Phorbol Acetate-Induced AP1 Pathway
Authors
Issue Date2004
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
Citation
Journal Of Virology, 2004, v. 78 n. 8, p. 4248-4267 How to Cite?
AbstractKaposi's sarcoma-associated herpesvirus (KSHV) maintains a latent infection in primary effusion lymphoma (PEL) cells, but treatment with tetradecanoyl phorbol acetate (TPA) can trigger the full lytic-cycle replication in some of these cells. During lytic-cycle replication, the KSHV-encoded replication and transcription activator (RTA or ORF50), the mRNA transport and accumulation protein (MTA), and the replication-associated protein (RAP) all play crucial roles in expression of downstream viral genes as well as in mediation of viral DNA replication. The cellular CCAAT/enhancer-binding protein alpha (C/EBPα) is induced in TPA-treated PEL cells and contributes to transactivation of the promoters for all of these genes through both direct binding and cooperative interactions with RTA and RAP targeted to upstream C/EBP sites. However, little is known about how RTA expression is triggered initially at the earliest stages after TPA induction when the C/EBPα levels are still limited. Treatment with TPA proved to significantly induce both AP1 DNA-binding activity and levels of activated phosphorylated cJUN in PEL cells and ectopic expression of cJUN-plus-cFOS-induced RTA protein expression in PEL cells. Cotransfected cJUN plus cFOS or TPA treatment transactivated the KSHV RTA, RAP, and MTA promoters in an AP1-binding site-dependent manner in all three promoters. Chromatin immunoprecipitation assays confirmed that cJUN associates with these KSHV target promoters in PEL cells as early as 4 h after TPA treatment. Furthermore, the KSHV RTA and RAP proteins both interact with cJUN or both cJUN and cFOS in vitro or by coimmunoprecipitation from induced PEL cells and enhance cJUN-plus-cFOS-mediated transactivation of these viral promoters. Both increased phosphorylated cJUN and AP1 DNA-binding activity was detected as early as 1 h after TPA treatment in PEL cells, suggesting that AP1 activity may be crucial for very early activation of the RAP, MTA, and RTA promoters during the KSHV lytic cycle. Finally, expression of RTA alone increased cJUN protein levels severalfold in DG75 cells but did not induce cJUN phosphorylation. Therefore, we suggest that the initiating effects of TPA via the AP1 pathway in PEL cells need to be amplified by RTA for full lytic-cycle induction.
Persistent Identifierhttp://hdl.handle.net/10722/49155
ISSN
2015 Impact Factor: 4.606
2015 SCImago Journal Rankings: 3.347
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWang, SEen_HK
dc.contributor.authorWu, FYen_HK
dc.contributor.authorChen, Hen_HK
dc.contributor.authorShamay, Men_HK
dc.contributor.authorZheng, Qen_HK
dc.contributor.authorHayward, GSen_HK
dc.date.accessioned2008-06-12T06:35:40Z-
dc.date.available2008-06-12T06:35:40Z-
dc.date.issued2004en_HK
dc.identifier.citationJournal Of Virology, 2004, v. 78 n. 8, p. 4248-4267en_HK
dc.identifier.issn0022-538Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/49155-
dc.description.abstractKaposi's sarcoma-associated herpesvirus (KSHV) maintains a latent infection in primary effusion lymphoma (PEL) cells, but treatment with tetradecanoyl phorbol acetate (TPA) can trigger the full lytic-cycle replication in some of these cells. During lytic-cycle replication, the KSHV-encoded replication and transcription activator (RTA or ORF50), the mRNA transport and accumulation protein (MTA), and the replication-associated protein (RAP) all play crucial roles in expression of downstream viral genes as well as in mediation of viral DNA replication. The cellular CCAAT/enhancer-binding protein alpha (C/EBPα) is induced in TPA-treated PEL cells and contributes to transactivation of the promoters for all of these genes through both direct binding and cooperative interactions with RTA and RAP targeted to upstream C/EBP sites. However, little is known about how RTA expression is triggered initially at the earliest stages after TPA induction when the C/EBPα levels are still limited. Treatment with TPA proved to significantly induce both AP1 DNA-binding activity and levels of activated phosphorylated cJUN in PEL cells and ectopic expression of cJUN-plus-cFOS-induced RTA protein expression in PEL cells. Cotransfected cJUN plus cFOS or TPA treatment transactivated the KSHV RTA, RAP, and MTA promoters in an AP1-binding site-dependent manner in all three promoters. Chromatin immunoprecipitation assays confirmed that cJUN associates with these KSHV target promoters in PEL cells as early as 4 h after TPA treatment. Furthermore, the KSHV RTA and RAP proteins both interact with cJUN or both cJUN and cFOS in vitro or by coimmunoprecipitation from induced PEL cells and enhance cJUN-plus-cFOS-mediated transactivation of these viral promoters. Both increased phosphorylated cJUN and AP1 DNA-binding activity was detected as early as 1 h after TPA treatment in PEL cells, suggesting that AP1 activity may be crucial for very early activation of the RAP, MTA, and RTA promoters during the KSHV lytic cycle. Finally, expression of RTA alone increased cJUN protein levels severalfold in DG75 cells but did not induce cJUN phosphorylation. Therefore, we suggest that the initiating effects of TPA via the AP1 pathway in PEL cells need to be amplified by RTA for full lytic-cycle induction.en_HK
dc.format.extent386 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/en_HK
dc.relation.ispartofJournal of Virologyen_HK
dc.rightsJournal of Virology. Copyright © American Society for Microbiology.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsCopyright © American Society for Microbiology, Journal of Virology, 2004, v. 78 n. 8, p. 4248-4267en_HK
dc.subject.meshGenes, Viralen_HK
dc.subject.meshHerpesvirus 8, Human - drug effects - genetics - physiologyen_HK
dc.subject.meshPromoter Regions (Genetics)en_HK
dc.subject.meshBasic-Leucine Zipper Transcription Factorsen_HK
dc.subject.meshBinding Sites - geneticsen_HK
dc.titleEarly Activation of the Kaposi's Sarcoma-Associated Herpesvirus RTA, RAP, and MTA Promoters by the Tetradecanoyl Phorbol Acetate-Induced AP1 Pathwayen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-538X&volume=78&issue=8&spage=4248&epage=4267&date=2004&atitle=Early+activation+of+the+Kaposi%27s+sarcoma-associated+herpesvirus+RTA,+RAP,+and+MTA+promoters+by+the+tetradecanoyl+phorbol+acetate-induced+AP1+pathwayen_HK
dc.identifier.emailChen, H:hlchen@hkucc.hku.hken_HK
dc.identifier.authorityChen, H=rp00383en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1128/JVI.78.8.4248-4267.2004en_HK
dc.identifier.pmid15047839-
dc.identifier.pmcidPMC374264en_HK
dc.identifier.scopuseid_2-s2.0-1842431602en_HK
dc.identifier.hkuros109262-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-1842431602&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume78en_HK
dc.identifier.issue8en_HK
dc.identifier.spage4248en_HK
dc.identifier.epage4267en_HK
dc.identifier.isiWOS:000220641600045-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWang, SE=8765314100en_HK
dc.identifier.scopusauthoridWu, FY=36991458700en_HK
dc.identifier.scopusauthoridChen, H=26643315400en_HK
dc.identifier.scopusauthoridShamay, M=6506101758en_HK
dc.identifier.scopusauthoridZheng, Q=8679121500en_HK
dc.identifier.scopusauthoridHayward, GS=7101602499en_HK

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