Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 4 (vIRF4/K10) is a novel interaction partner of CSL/CBF1, the major downstream effector of Notch signaling.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620801
Title:
Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 4 (vIRF4/K10) is a novel interaction partner of CSL/CBF1, the major downstream effector of Notch signaling.
Authors:
Heinzelmann, Katharina; Scholz, Barbara A; Nowak, Agnes; Fossum, Even; Kremmer, Elisabeth; Haas, Juergen; Frank, Ronald; Kempkes, Bettina
Abstract:
In cells infected with the Kaposi's sarcoma-associated herpesvirus (KSHV), CSL/CBF1 signaling is essential for viral replication and promotes the survival of KSHV-infected cells. CSL/CBF1 is a DNA adaptor molecule which recruits coactivator and corepressor complexes to regulate viral and cellular gene transcription and which is a major downstream effector molecule of activated Notch. The interaction of KSHV RTA and LANA with CSL/CBF1 has been shown to balance the lytic and latent viral life cycle. Here we report that a third KSHV protein, viral interferon regulatory factor 4 (vIRF4/K10), but none of the three other KSHV-encoded vIRFs, interacts with CSL/CBF1. Two regions of vIRF4 with dissimilar affinities contribute to CSL/CBF1 binding. Similar to Notch, vIRF4 targets the hydrophobic pocket in the beta trefoil domain of CSL/CBF1 through a short peptide motif which closely resembles a motif found in Notch but does not strictly follow the ΦWΦP consensus conserved in human and mouse Notch proteins. Our results suggest that vIRF4 might compete with Notch for CSL/CBF1 binding and signaling.
Affiliation:
Helmholtz Centre for infection research. Inhoffenstr. 7. 38124 Braunschweig, Germany.
Citation:
Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 4 (vIRF4/K10) is a novel interaction partner of CSL/CBF1, the major downstream effector of Notch signaling. 2010, 84 (23):12255-64 J. Virol.
Journal:
Journal of virology
Issue Date:
Dec-2010
URI:
http://hdl.handle.net/10033/620801
DOI:
10.1128/JVI.01484-10
PubMed ID:
20861242
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.authorHeinzelmann, Katharinaen
dc.contributor.authorScholz, Barbara Aen
dc.contributor.authorNowak, Agnesen
dc.contributor.authorFossum, Evenen
dc.contributor.authorKremmer, Elisabethen
dc.contributor.authorHaas, Juergenen
dc.contributor.authorFrank, Ronalden
dc.contributor.authorKempkes, Bettinaen
dc.date.accessioned2017-02-02T14:21:56Z-
dc.date.available2017-02-02T14:21:56Z-
dc.date.issued2010-12-
dc.identifier.citationKaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 4 (vIRF4/K10) is a novel interaction partner of CSL/CBF1, the major downstream effector of Notch signaling. 2010, 84 (23):12255-64 J. Virol.en
dc.identifier.issn1098-5514-
dc.identifier.pmid20861242-
dc.identifier.doi10.1128/JVI.01484-10-
dc.identifier.urihttp://hdl.handle.net/10033/620801-
dc.description.abstractIn cells infected with the Kaposi's sarcoma-associated herpesvirus (KSHV), CSL/CBF1 signaling is essential for viral replication and promotes the survival of KSHV-infected cells. CSL/CBF1 is a DNA adaptor molecule which recruits coactivator and corepressor complexes to regulate viral and cellular gene transcription and which is a major downstream effector molecule of activated Notch. The interaction of KSHV RTA and LANA with CSL/CBF1 has been shown to balance the lytic and latent viral life cycle. Here we report that a third KSHV protein, viral interferon regulatory factor 4 (vIRF4/K10), but none of the three other KSHV-encoded vIRFs, interacts with CSL/CBF1. Two regions of vIRF4 with dissimilar affinities contribute to CSL/CBF1 binding. Similar to Notch, vIRF4 targets the hydrophobic pocket in the beta trefoil domain of CSL/CBF1 through a short peptide motif which closely resembles a motif found in Notch but does not strictly follow the ΦWΦP consensus conserved in human and mouse Notch proteins. Our results suggest that vIRF4 might compete with Notch for CSL/CBF1 binding and signaling.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshBinding, Competitiveen
dc.subject.meshCell Line, Tumoren
dc.subject.meshChromatography, Affinityen
dc.subject.meshDNA Primersen
dc.subject.meshElectrophoresis, Polyacrylamide Gelen
dc.subject.meshElectrophoretic Mobility Shift Assayen
dc.subject.meshHerpesvirus 8, Humanen
dc.subject.meshHumansen
dc.subject.meshImmunoblottingen
dc.subject.meshImmunoglobulin J Recombination Signal Sequence-Binding Proteinen
dc.subject.meshImmunoprecipitationen
dc.subject.meshInterferon Regulatory Factorsen
dc.subject.meshPlasmidsen
dc.subject.meshProtein Bindingen
dc.subject.meshReceptors, Notchen
dc.subject.meshSignal Transductionen
dc.subject.meshTwo-Hybrid System Techniquesen
dc.subject.meshViral Proteinsen
dc.titleKaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 4 (vIRF4/K10) is a novel interaction partner of CSL/CBF1, the major downstream effector of Notch signaling.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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