In:
Journal of Virology, American Society for Microbiology, Vol. 80, No. 21 ( 2006-11), p. 10772-10786
Kurzfassung:
The Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated
nuclear antigen 1 (LANA-1) is required for the replication of episomal viral genomes. Regions in its N-terminal and C-terminal domains mediate
the interaction with host cell chromatin. Several cellular nuclear proteins, e.g., BRD2/RING3, histones H2A and H2B, MeCP2, DEK, and
HP1α, have been suggested to mediate this interaction. In this work, we identify the double-bromodomain proteins BRD4 and BRD3/ORFX as
additional LANA-1 interaction partners. The carboxy-terminal region of the short variant of BRD4 (BRD4 S ) containing the highly
conserved extraterminal domain directly interacts with an element in the LANA-1 carboxy-terminal domain. We show that ectopically expressed
BRD4 S and BRD2/RING3 delay progression into the S phase of
the cell cycle in epithelial and B-cell lines and increase cyclin E promoter activity. LANA-1 partly releases epithelial and B cells from a
BRD4 S - and BRD2/RING3-induced G 1 cell cycle
arrest and also promotes S-phase entry in the presence of BRD4 S and BRD2/RING3. This is accompanied by a reduction in
BRD4 S -mediated cyclin E promoter activity. Our data are in
keeping with the notion that the direct interaction of KSHV LANA-1 with BRD4 and other BRD proteins could play a role in the G 1 /S
phase-promoting functions of KSHV LANA-1. Further, our data support a model in which the LANA-1 C terminus contributes to a functional
attachment to acetylated histones H3 and H4 via BRD4 and BRD2, in addition to the recently demonstrated direct interaction (A.
J. Barbera, J. V. Chodaparambil, B. Kelley-Clarke, V. Joukov, J. C. Walter, K. Luger, and K. M. Kaye, Science
311:856-861, 2006) of the LANA-1 N terminus with histones H2A and
H2B.
Materialart:
Online-Ressource
ISSN:
0022-538X
,
1098-5514
DOI:
10.1128/JVI.00804-06
Sprache:
Englisch
Verlag:
American Society for Microbiology
Publikationsdatum:
2006
ZDB Id:
1495529-5
