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2003 ; 77
(22
): 12243-51
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Borna disease virus phosphoprotein represses p53-mediated transcriptional
activity by interference with HMGB1
#MMPMID14581561
Zhang G
; Kobayashi T
; Kamitani W
; Komoto S
; Yamashita M
; Baba S
; Yanai H
; Ikuta K
; Tomonaga K
J Virol
2003[Nov]; 77
(22
): 12243-51
PMID14581561
show ga
Borna disease virus (BDV) is a noncytolytic, neurotropic RNA virus that has a
broad host range in warm-blooded animals, probably including humans. Recently, it
was demonstrated that a 24-kDa phosphoprotein (P) of BDV directly binds to a
multifunctional protein, amphoterin-HMGB1, and inhibits its function in cultured
neural cells (W. Kamitani, Y. Shoya, T. Kobayashi, M. Watanabe, B. J. Lee, G.
Zhang, K. Tomonaga, and K. Ikuta, J. Virol. 75:8742-8751, 2001). This observation
suggested that expression of BDV P may cause deleterious effects in cellular
functions by interference with HMGB1. In this study, we further investigated the
significance of the binding between P and HMGB1. We demonstrated that P directly
binds to the A-box domain on HMGB1, which is also responsible for interaction
with a tumor suppression factor, p53. Recent works have demonstrated that binding
between HMGB1 and p53 enhances p53-mediated transcriptional activity. Thus, we
examined whether BDV P affects the transcriptional activity of p53 by
interference with HMGB1. Mammalian two-hybrid analysis revealed that p53 and P
competitively interfere with the binding of each protein to HMGB1 in a
p53-deficient cell line, NCI-H1299. In addition, P was able to significantly
decrease p53-mediated transcriptional activation of the cyclin G promoter.
Furthermore, we showed that activation of p21(waf1) expression was repressed in
cyclosporine-treated BDV-infected cells, as well as p53-transduced NCI-H1299
cells. These results suggested that BDV P may be a unique inhibitor of p53
activity via binding to HMGB1.
|*Transcriptional Activation
[MESH]
|Animals
[MESH]
|Binding, Competitive
[MESH]
|Borna disease virus/*physiology
[MESH]
|Cell Line, Tumor
[MESH]
|Cyclin G
[MESH]
|Cyclin G1
[MESH]
|Cyclin-Dependent Kinase Inhibitor p21
[MESH]
|Cyclins/genetics
[MESH]
|DNA/metabolism
[MESH]
|HMGB1 Protein/chemistry/*metabolism
[MESH]
|Rats
[MESH]
|Tumor Suppressor Protein p53/*antagonists & inhibitors/physiology
[MESH]