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.
J. Virol. 84, 12255-12264 (2010)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Gamma-secretase inhibitor; Lytic switch protein; RBP-J-Kappa; Nuclear antigen; Transcriptional activation; Crystal-structure; Tumor-cells; In-vitro; CSL; Pathway
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2010
Prepublished im Jahr
HGF-Berichtsjahr
2010
ISSN (print) / ISBN
0022-538X
e-ISSN
1098-5514
ISBN
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Konferenztitel
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Konferenzband
Quellenangaben
Band: 84,
Heft: 23,
Seiten: 12255-12264
Artikelnummer: ,
Supplement: ,
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Verlag
American Society for Microbiology (ASM)
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0000-00-00
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Prüfer
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0000-00-00
Anmelder/Inhaber
weitere Inhaber
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Begutachtungsstatus
Peer reviewed
POF Topic(s)
30203 - Molecular Targets and Therapies
Forschungsfeld(er)
Immune Response and Infection
PSP-Element(e)
G-501500-002
G-501700-003
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Copyright
Erfassungsdatum
2010-11-30