Induction of Epstein-Barr virus oncoprotein LMP1 by transcription factors AP-2 and early B cell factor

Takayuki Murata, Chieko Noda, Yohei Narita, Takahiro Watanabe, Masahiro Yoshida, Keiji Ashio, Yoshitaka Sato, Fumi Goshima, Teru Kanda, Hironori Yoshiyama, Tatsuya Tsurumi, Hiroshi Kimura

Research output: Contribution to journalArticle

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Abstract

Latent membrane protein 1 (LMP1) is a major oncogene essential for primary B cell transformation by Epstein-Barr virus (EBV). Previous studies suggested that some transcription factors, such as PU.1, RBP-Jκ, NF-κB, and STAT, are involved in this expression, but the underlying mechanism is unclear. Here, we identified binding sites for PAX5, AP-2, and EBF in the proximal LMP1 promoter (ED-L1p). We first confirmed the significance of PU.1 and POU domain transcription factor binding for activation of the promoter in latency III. We then focused on the transcription factors AP-2 and early B cell factor (EBF). Interestingly, among the three AP-2-binding sites in the LMP1 promoter, two motifs were also bound by EBF. Overexpression, knockdown, and mutagenesis in the context of the viral genome indicated that AP-2 plays an important role in LMP1 expression in latency II in epithelial cells. In latency III B cells, on the other hand, the B cell-specific transcription factor EBF binds to the ED-L1p and activates LMP1 transcription from the promoter.

Original languageEnglish
Pages (from-to)3873-3889
Number of pages17
JournalJournal of Virology
Volume90
Issue number8
DOIs
Publication statusPublished - 01-04-2016

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Transcription Factor AP-2
Human herpesvirus 4
Oncogene Proteins
membrane proteins
B-lymphocytes
B-Lymphocytes
transcription factors
Membrane Proteins
promoter regions
PAX5 Transcription Factor
POU Domain Factors
Binding Sites
binding sites
Viral Genome
Human Herpesvirus 4
Oncogenes
oncogenes
Mutagenesis
3'-(1-butylphosphoryl)adenosine
Epstein-Barr virus EBV-associated membrane antigen

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Murata, Takayuki ; Noda, Chieko ; Narita, Yohei ; Watanabe, Takahiro ; Yoshida, Masahiro ; Ashio, Keiji ; Sato, Yoshitaka ; Goshima, Fumi ; Kanda, Teru ; Yoshiyama, Hironori ; Tsurumi, Tatsuya ; Kimura, Hiroshi. / Induction of Epstein-Barr virus oncoprotein LMP1 by transcription factors AP-2 and early B cell factor. In: Journal of Virology. 2016 ; Vol. 90, No. 8. pp. 3873-3889.
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Murata, T, Noda, C, Narita, Y, Watanabe, T, Yoshida, M, Ashio, K, Sato, Y, Goshima, F, Kanda, T, Yoshiyama, H, Tsurumi, T & Kimura, H 2016, 'Induction of Epstein-Barr virus oncoprotein LMP1 by transcription factors AP-2 and early B cell factor', Journal of Virology, vol. 90, no. 8, pp. 3873-3889. https://doi.org/10.1128/JVI.03227-15

Induction of Epstein-Barr virus oncoprotein LMP1 by transcription factors AP-2 and early B cell factor. / Murata, Takayuki; Noda, Chieko; Narita, Yohei; Watanabe, Takahiro; Yoshida, Masahiro; Ashio, Keiji; Sato, Yoshitaka; Goshima, Fumi; Kanda, Teru; Yoshiyama, Hironori; Tsurumi, Tatsuya; Kimura, Hiroshi.

In: Journal of Virology, Vol. 90, No. 8, 01.04.2016, p. 3873-3889.

Research output: Contribution to journalArticle

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T1 - Induction of Epstein-Barr virus oncoprotein LMP1 by transcription factors AP-2 and early B cell factor

AU - Murata, Takayuki

AU - Noda, Chieko

AU - Narita, Yohei

AU - Watanabe, Takahiro

AU - Yoshida, Masahiro

AU - Ashio, Keiji

AU - Sato, Yoshitaka

AU - Goshima, Fumi

AU - Kanda, Teru

AU - Yoshiyama, Hironori

AU - Tsurumi, Tatsuya

AU - Kimura, Hiroshi

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Latent membrane protein 1 (LMP1) is a major oncogene essential for primary B cell transformation by Epstein-Barr virus (EBV). Previous studies suggested that some transcription factors, such as PU.1, RBP-Jκ, NF-κB, and STAT, are involved in this expression, but the underlying mechanism is unclear. Here, we identified binding sites for PAX5, AP-2, and EBF in the proximal LMP1 promoter (ED-L1p). We first confirmed the significance of PU.1 and POU domain transcription factor binding for activation of the promoter in latency III. We then focused on the transcription factors AP-2 and early B cell factor (EBF). Interestingly, among the three AP-2-binding sites in the LMP1 promoter, two motifs were also bound by EBF. Overexpression, knockdown, and mutagenesis in the context of the viral genome indicated that AP-2 plays an important role in LMP1 expression in latency II in epithelial cells. In latency III B cells, on the other hand, the B cell-specific transcription factor EBF binds to the ED-L1p and activates LMP1 transcription from the promoter.

AB - Latent membrane protein 1 (LMP1) is a major oncogene essential for primary B cell transformation by Epstein-Barr virus (EBV). Previous studies suggested that some transcription factors, such as PU.1, RBP-Jκ, NF-κB, and STAT, are involved in this expression, but the underlying mechanism is unclear. Here, we identified binding sites for PAX5, AP-2, and EBF in the proximal LMP1 promoter (ED-L1p). We first confirmed the significance of PU.1 and POU domain transcription factor binding for activation of the promoter in latency III. We then focused on the transcription factors AP-2 and early B cell factor (EBF). Interestingly, among the three AP-2-binding sites in the LMP1 promoter, two motifs were also bound by EBF. Overexpression, knockdown, and mutagenesis in the context of the viral genome indicated that AP-2 plays an important role in LMP1 expression in latency II in epithelial cells. In latency III B cells, on the other hand, the B cell-specific transcription factor EBF binds to the ED-L1p and activates LMP1 transcription from the promoter.

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