Suppression of INK4a/ARF expression by EBV protein EBNA3C

• Project/Area Number: 20590464
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Hokkaido University
• Principal Investigator: MARUO Seiji Hokkaido University, 遺伝子病制御研究所, 准教授 (70292018)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: EBウイルス / 形質転換 / 不死化 / がん抑制遺伝子 / エピジェネティクス / INK4a/ARF / EBNA3C / EBNA3A / RBP-Jκ / 癌抑制遺伝子 / INK4a / ARF / ヒストン修飾

Research Abstract

In this study, the mechanism underlying EBNA3C suppression of the INK4a/ARF expression was analyzed. We clarified that (1) EBNA3C does not influence the DNA methylation status of the INK4a/ARF promoters. (2) EBNA3C changes histone modifications of the p16 (INK4a) locus from active state to silent state. (3) EBNA3C association with RBP-Jkappa is essential for EBNA3C to function. These results suggest that EBNA3C regulates epigenetic histone modifications of the INK4a/ARF locus.

Research Products

• [Journal Article] Epstein-Barr virus nuclear antigens 3C and 3A maintain lymphoblastoid cell growth by repressing p16INK4A and p14ARF expression. (2011)
  • Author(s): Maruo S, Zhao B, Johannsen E, Kieff E, Zou J, Takada K.
  • Journal Title: Proc Natl Acad Sci USA. 108 Pages: 1919-1924
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus nuclear antigen 3C regulated genes in lymphoblastoid cell lines. (2011)
  • Author(s): Zhao B, Mar JC, Maruo S, Lee S, Gewurz BE, Johannsen E, Holton K, Rubio R, Takada K, Quackenbush J, Kieff E.
  • Journal Title: Proc Natl Acad Sci USA. 108 Pages: 337-342
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus nuclear antigen 3C regulated genes in lymphoblastoid cell lines. (2011)
  • Author(s): Bo Zhao
  • Journal Title: Proc Natl Acad Sci USA Volume: 108 Pages: 337-342
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus nuclear antigens 3C and 3A maintain lymphoblastoid cell growth by repressing p16^<INK4A> and p14^<ARF> expression. (2011)
  • Author(s): Seiji Maruo
  • Journal Title: Proc Natl Acad Sci USA Volume: 108 Pages: 1909-1924
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus-encoded Bcl-2 homologue functions as a survival factor in Wp-restricted Burkitt lymphoma cell line P3HR-1. (2010)
  • Author(s): Watanabe A, Maruo S, Ito T, Ito M, Katsumura KR, Takada K.
  • Journal Title: J Virol. 84 Pages: 2893-2901
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus-encoded Bcl-2 homologue functions as a survival factor in Wp-restricted Burkitt lymphoma cell line P3HR-1. (2010)
  • Author(s): Ami Watanabe
  • Journal Title: Journal of Virology 84 Pages: 2893-2901
  • Peer Reviewed
• [Journal Article] EBNA3C interacts with Gadd34 and counteracts the unfolded protein response. (2009)
  • Author(s): Garrido JL, Maruo S, Takada K, Rosendorff A.
  • Journal Title: Virol J. 6 Pages: 231-231
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus nuclear protein 3C domains necessary for lymphoblastoid cell growth : interaction with RBP-Jkappa regulates TCL1. (2009)
  • Author(s): Lee S, Sakakibara S, Maruo S, Zhao B, Calderwood MA, Holthaus AM, Lai CY, Takada K, Kieff E, Johannsen E.
  • Journal Title: J Virol. 83 Pages: 12368-12377
  • Peer Reviewed
• [Journal Article] Quantitative evaluation of the role of Epstein-Barr virus immediate-early protein BZLF1 in B-cell transformation. (2009)
  • Author(s): Katsumura KR, Maruo S, Wu Y, Kanda T, Takada K.
  • Journal Title: J Gen Virol. 90 Pages: 2331-2341
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus nuclear protein EBNA3C residues critical for maintaining lymphoblastoid cell growth. (2009)
  • Author(s): Maruo S, Wu Y, Ito T, Kanda T, Kieff ED, Takada K.
  • Journal Title: Proc Natl Acad Sci USA. 106 Pages: 4419-4424
  • Peer Reviewed
• [Journal Article] Quantitative evaluation of the role of Epstein-Barr virus immediate-early protein BZLF1 in B-cell transformation (2009)
  • Author(s): Koichi R.Katsumura
  • Journal Title: Journal of General Virology 90 Pages: 2331-2341
  • Peer Reviewed
• [Journal Article] Epstein-Barr Virus Nuclear Protein 3C Domains Necessary for Lymphob lastoid Cell Growth ; Interaction with RBP-J {kappa} Regulates TCL1. (2009)
  • Author(s): Sungwook Lee
  • Journal Title: Journal of Virology 83 Pages: 12368-12377
  • Peer Reviewed
• [Journal Article] EBNA3C interacts with Gadd34 and counteracts the unfolded protein response. (2009)
  • Author(s): Jose L.Garrido
  • Journal Title: Virology Journal 6 Pages: 231-231
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus nuclear protein EBNA3C residues critical for maintaining lymphoblastoid cell growth (2009)
  • Author(s): Seiji Maruo
  • Journal Title: Proc Natl Acad Sci USA 106 Pages: 4419-4424
  • Peer Reviewed
• [Presentation] Epstein-Barr virus nuclear protein EBNA3C contributes to the growth of EBV-transformed B cells through repressing p16(INK4A) and p14(ARF) expression (2010)
  • Author(s): 丸尾聖爾
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド(神戸)
  • Year and Date: 2010-12-09
• [Presentation] Epstein-Barr virus nuclear protein EBNA3C contributes to the growth of EBV-transformed B cells through repressing p16(INK4A)and p14(ARF) expression (2010)
  • Author(s): Seiji Maruo
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド(神戸)
  • Year and Date: 2010-12-09
• [Presentation] EBウイルス核蛋白質EBNA3Cによるエピジェネティックなp16(INK4A)の発現抑制機構 (2010)
  • Author(s): 丸尾聖爾
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: あわぎんホール(徳島)
  • Year and Date: 2010-11-09
• [Presentation] EBウイルスのコードするBcl-2ホモログはバーキットリンパ腫細胞株P3HR-1の生存に必須である (2009)
  • Author(s): 渡邊亜美
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 都市センターホテル(東京)
  • Year and Date: 2009-10-27
• [Presentation] EBウイルスのコードするBcl-2ホモログはバーキットリンパ腫細胞株P3HR-1の生存に必須である (2009)
  • Author(s): 渡邊亜美
  • Organizer: 第57回 日本ウイルス学会学術集会
  • Place of Presentation: 都市センターホテル(東京)
  • Year and Date: 2009-10-27
• [Presentation] Roles of Epstein-Barr virus nuclear protein EBNAs in B-cell growth transformation (2009)
  • Author(s): 丸尾聖爾
  • Organizer: 68th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2009-10-01
• [Presentation] Roles of Epstein-Barr virus nuclear protein EBNAs in B-cell growth transformation. (2009)
  • Author(s): Seiji Maruo
  • Organizer: 68th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2009-10-01
• [Presentation] EBNA3C transcriptional regulation through RBP-Jkappa is critical for growth maintenance of lymphoblastoid cells (2008)
  • Author(s): 丸尾聖爾
  • Organizer: 13th Biennial Conference of the International Association for Research on Epstein-Barr Virus And Associated Diseases
  • Place of Presentation: Baiyun Conference center, Guangzhou, China
  • Year and Date: 2008-11-08
• [Presentation] EBウイルス核蛋白質EBNA3CはINK4A/ARFを抑制することによりLCLの増殖維持に寄与する (2008)
  • Author(s): 丸尾聖爾
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2008-10-26
• [Presentation] EBウイルス核蛋白質EBNA3CはINK4A/ARFを抑制することによりLCLの増殖維持に寄与する (2008)
  • Author(s): 丸尾聖爾
  • Organizer: 日本ウイルス学会(第56回学術集会)
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2008-10-26
• [Remarks] ホームページ等