The interaction of the gammaherpesvirus 68 orf73 protein with cellular BET proteins affects the activation of cell cycle promoters.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620745
Title:
The interaction of the gammaherpesvirus 68 orf73 protein with cellular BET proteins affects the activation of cell cycle promoters.
Authors:
Ottinger, Matthias; Pliquet, Daniel; Christalla, Thomas; Frank, Ronald; Stewart, James P; Schulz, Thomas F
Abstract:
Infection of mice with murine gammaherpesvirus 68 (MHV-68) provides a valuable animal model for gamma-2 herpesvirus (rhadinovirus) infection and pathogenesis. The MHV-68 orf73 protein has been shown to be required for the establishment of viral latency in vivo. This study describes a novel transcriptional activation function of the MHV-68 orf73 protein and identifies the cellular bromodomain containing BET proteins Brd2/RING3, Brd3/ORFX, and BRD4 as interaction partners for the MHV-68 orf73 protein. BET protein members are known to interact with acetylated histones, and Brd2 and Brd4 have been implicated in fundamental cellular processes, including cell cycle regulation and transcriptional regulation. Using MHV-68 orf73 peptide array assays, we identified Brd2 and Brd4 interaction sites in the orf73 protein. Mutation of one binding site led to a loss of the interaction with Brd2/4 but not the retinoblastoma protein Rb, to impaired chromatin association, and to a decreased ability to activate the BET-responsive cyclin D1, D2, and E promoters. The results therefore pinpoint the binding site for Brd2/4 in a rhadinoviral orf73 protein and suggest that the recruitment of a member of the BET protein family allows the MHV-68 orf73 protein to activate the promoters of G(1)/S cyclins. These findings point to parallels between the transcriptional activator functions of rhadinoviral orf73 proteins and papillomavirus E2 proteins.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
The interaction of the gammaherpesvirus 68 orf73 protein with cellular BET proteins affects the activation of cell cycle promoters. 2009, 83 (9):4423-34 J. Virol.
Journal:
Journal of virology
Issue Date:
May-2009
URI:
http://hdl.handle.net/10033/620745
DOI:
10.1128/JVI.02274-08
PubMed ID:
19244327
Type:
Article
Language:
en
ISSN:
1098-5514
Appears in Collections:
Publications of the research group Chemical Biology (CBIO)

Full metadata record

DC FieldValue Language
dc.contributor.authorOttinger, Matthiasen
dc.contributor.authorPliquet, Danielen
dc.contributor.authorChristalla, Thomasen
dc.contributor.authorFrank, Ronalden
dc.contributor.authorStewart, James Pen
dc.contributor.authorSchulz, Thomas Fen
dc.date.accessioned2017-01-24T15:02:03Z-
dc.date.available2017-01-24T15:02:03Z-
dc.date.issued2009-05-
dc.identifier.citationThe interaction of the gammaherpesvirus 68 orf73 protein with cellular BET proteins affects the activation of cell cycle promoters. 2009, 83 (9):4423-34 J. Virol.en
dc.identifier.issn1098-5514-
dc.identifier.pmid19244327-
dc.identifier.doi10.1128/JVI.02274-08-
dc.identifier.urihttp://hdl.handle.net/10033/620745-
dc.description.abstractInfection of mice with murine gammaherpesvirus 68 (MHV-68) provides a valuable animal model for gamma-2 herpesvirus (rhadinovirus) infection and pathogenesis. The MHV-68 orf73 protein has been shown to be required for the establishment of viral latency in vivo. This study describes a novel transcriptional activation function of the MHV-68 orf73 protein and identifies the cellular bromodomain containing BET proteins Brd2/RING3, Brd3/ORFX, and BRD4 as interaction partners for the MHV-68 orf73 protein. BET protein members are known to interact with acetylated histones, and Brd2 and Brd4 have been implicated in fundamental cellular processes, including cell cycle regulation and transcriptional regulation. Using MHV-68 orf73 peptide array assays, we identified Brd2 and Brd4 interaction sites in the orf73 protein. Mutation of one binding site led to a loss of the interaction with Brd2/4 but not the retinoblastoma protein Rb, to impaired chromatin association, and to a decreased ability to activate the BET-responsive cyclin D1, D2, and E promoters. The results therefore pinpoint the binding site for Brd2/4 in a rhadinoviral orf73 protein and suggest that the recruitment of a member of the BET protein family allows the MHV-68 orf73 protein to activate the promoters of G(1)/S cyclins. These findings point to parallels between the transcriptional activator functions of rhadinoviral orf73 proteins and papillomavirus E2 proteins.en
dc.language.isoenen
dc.subject.meshAmino Acid Sequenceen
dc.subject.meshAnimalsen
dc.subject.meshBinding Sitesen
dc.subject.meshCell Cycleen
dc.subject.meshCell Lineen
dc.subject.meshCell Nucleusen
dc.subject.meshChromatinen
dc.subject.meshHerpesviridaeen
dc.subject.meshHumansen
dc.subject.meshMiceen
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshMutationen
dc.subject.meshPromoter Regions, Geneticen
dc.subject.meshProtein Bindingen
dc.subject.meshProtein-Serine-Threonine Kinasesen
dc.subject.meshRetinoblastoma Proteinen
dc.subject.meshSequence Alignmenten
dc.subject.meshTranscription, Geneticen
dc.subject.meshViral Proteinsen
dc.titleThe interaction of the gammaherpesvirus 68 orf73 protein with cellular BET proteins affects the activation of cell cycle promoters.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalJournal of virologyen
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