Borna Disease Virus Phosphoprotein Represses p53-Mediated Transcriptional Activity by Interference with HMGB1

Guoqi Zhang, Takeshi Kobayashi, Wataru Kamitani, Satoshi Komoto, Makiko Yamashita, Satoko Baba, Hideyuki Yanai, Kazuyoshi Ikuta, Keizo Tomonaga

Research output: Contribution to journalArticle

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Abstract

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 p21waf1 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.

Original languageEnglish
Pages (from-to)12243-12251
Number of pages9
JournalJournal of Virology
Volume77
Issue number22
DOIs
Publication statusPublished - 01-11-2003

Fingerprint

Borna disease virus
HMGB1 Protein
phosphoproteins
Phosphoproteins
crossover interference
two hybrid system techniques
cyclosporine
Cyclin G
cyclins
transcriptional activation
host range
binding proteins
neurons
Host Specificity
RNA Viruses
promoter regions
cell lines
cells
Transcriptional Activation
Cyclosporine

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Zhang, Guoqi ; Kobayashi, Takeshi ; Kamitani, Wataru ; Komoto, Satoshi ; Yamashita, Makiko ; Baba, Satoko ; Yanai, Hideyuki ; Ikuta, Kazuyoshi ; Tomonaga, Keizo. / Borna Disease Virus Phosphoprotein Represses p53-Mediated Transcriptional Activity by Interference with HMGB1. In: Journal of Virology. 2003 ; Vol. 77, No. 22. pp. 12243-12251.
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abstract = "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 p21waf1 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.",
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Zhang, G, Kobayashi, T, Kamitani, W, Komoto, S, Yamashita, M, Baba, S, Yanai, H, Ikuta, K & Tomonaga, K 2003, 'Borna Disease Virus Phosphoprotein Represses p53-Mediated Transcriptional Activity by Interference with HMGB1', Journal of Virology, vol. 77, no. 22, pp. 12243-12251. https://doi.org/10.1128/JVI.77.22.12243-12251.2003

Borna Disease Virus Phosphoprotein Represses p53-Mediated Transcriptional Activity by Interference with HMGB1. / Zhang, Guoqi; Kobayashi, Takeshi; Kamitani, Wataru; Komoto, Satoshi; Yamashita, Makiko; Baba, Satoko; Yanai, Hideyuki; Ikuta, Kazuyoshi; Tomonaga, Keizo.

In: Journal of Virology, Vol. 77, No. 22, 01.11.2003, p. 12243-12251.

Research output: Contribution to journalArticle

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T1 - Borna Disease Virus Phosphoprotein Represses p53-Mediated Transcriptional Activity by Interference with HMGB1

AU - Zhang, Guoqi

AU - Kobayashi, Takeshi

AU - Kamitani, Wataru

AU - Komoto, Satoshi

AU - Yamashita, Makiko

AU - Baba, Satoko

AU - Yanai, Hideyuki

AU - Ikuta, Kazuyoshi

AU - Tomonaga, Keizo

PY - 2003/11/1

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N2 - 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 p21waf1 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.

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