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.
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.
Heinzelmann
Katharina
K
Department of Gene Vectors, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany.
Scholz
Barbara A
BA
Nowak
Agnes
A
Fossum
Even
E
Kremmer
Elisabeth
E
Haas
Juergen
J
Frank
Ronald
R
Kempkes
Bettina
B
D001667:Binding, Competitive; D045744:Cell Line, Tumor; D002846:Chromatography, Affinity; D017931:DNA Primers / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D024202:Electrophoretic Mobility Shift Assay; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism*; D047468:Immunoprecipitation; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000378:metabolism*
D017931:DNA Primers; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D050835:Interferon Regulatory Factors; C497570:RBPJ protein, human; D051880:Receptors, Notch; D014764:Viral Proteins; C413486:viral interferon regulatory factors