Functional analysis of a novel E3 ubiquitin ligase family.

• Project/Area Number: 18590482
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: ISHIDO Satoshi The Institute of Physical and Chemical Research, Infectious Immunity Team, Team Leader (10273781)
• Co-Investigator(Kenkyū-buntansha): HOSHINO Mari RIKEN, Infectious Immunity Team, Researcher (10313511)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
• Keywords: ubiauitin / antigen presentation / ubiauitin ligase / MHC class II / endocvtosis / B7-2 / knockout mouse / immunosuppressor / B7-2 / 遺伝子改変マウス / エンドサイトーシス / 分解

Research Abstract

The presence of post-translational regulation of MHC class II (MHC II) under physiological conditions has been demonstrated recently in dendritic cells (DCs) that potently function as antigen-presenting cells (APCs). Here, we report that MARCH-I, an E3 ubiquitin ligase, plays a pivotal role in the post-translational regulation of MHC H in B cells. MARCH-I expression was particularly high in B cells, and the forced expression of MARCH-I induced the ubiquitination of MHC II. In B cells from MARCH-I-deficient mice (MARCH-I KO), the half-life of surface MHC II was prolonged and the ubiquitinated form of MHC II completely disappeared. In addition, MARCH-I-deficient B cells highly expressed exogenous-antigen-loaded MHC II on their surface and showed high ability to present exogenous antigens. These results suggest that the function of MHC II in B cells is regulated through ubiquitination by MARCH-I

Research Products

• [Journal Article] An Excellent Monitoring System for Surface Ubiquitination-Induced Internalization in Mammals (2008)
  • Author(s): Goto, E., Mito-Yoshida, M., Uematsu, M., Aoki, M., Matsuki, Y., Ohmura-Hoshino, M., Hotta, H., Miyagishi, M., Ishido, S.
  • Journal Title: PLoS ONE 3
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] An Excellent Monitoring System for Surface Ubiquitination-Induced Internalization in Mammals (2008)
  • Author(s): Goto, E., Mito-Yoshida, M., Uematsu, M., Aoki, M., Matsuki, Y., Ohmura-Hoshino, M., Hotta, H., Miyagishi, M., Ishido, S.
  • Journal Title: PloS ONE 3(1)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] An Excellent Monitoring System for Surface Ubiquitination-Induced Internalization in Mammals (2008)
  • Author(s): 後藤 栄治、石戸 聡
  • Journal Title: PLOS ONE 3(1)
  • Peer Reviewed
• [Journal Article] Novel regulation of MHC class II function in B cells. (2007)
  • Author(s): Matsuki, Y., Ohmura-Hoshino, M., Goto, E., Aoki, M., Mito-Yoshida, M., Uematsu, M., Hasegawa, T., Koseki, H., Ohara, O., Nakayama, M., Toyooka, K., Matsuoka, K., Hotta, H., Yamamoto, A., Ishido, S.
  • Journal Title: EMBO J 26
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Novel regulation fo MHC class II function in Bcells. (2007)
  • Author(s): Matsuki, Y., Ohmura-Hoshino, M., Goto, E., Aoki, M., Mito-Yoshida, M., Uematsu, M., Hasegawa, T., Koseki, H., Ohara, O., Nakayama, M., Toyooka, K., Matsuoka, K., Hotta, H., Yamamoto, A., Ishido, S.
  • Journal Title: EMBO J. 2007 Feb 7 ; 26(3) 25 Pages: 846-54
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 主要組織適合抗原の新たな制御分子群 (2007)
  • Author(s): 後藤栄治、星野真理、松木洋平、水戸麻理、青木雅美、植松未香、石戸聡、
  • Journal Title: 第30回日本分子生物学会・第80回日本生化学学会合同大会(BMB2007)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] New players for regulatin of MHC function (2007)
  • Author(s): Ishido, S. Ohmura-Hoshino, M., Goto, E., Matsuki, Y., Aoki, M., Mito-Yoshida, M., Uematsu, M.
  • Journal Title: International Symposium on Membrane Traffic
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 樹状細胞の分化に重要な役割を持つMARCH-I分子 (2007)
  • Author(s): 星野真理、松木洋平、後藤栄治、水戸麻理、青木雅美、植松未香、石戸聡、
  • Journal Title: 日本免疫学会総会
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] カポジ肉腫関連ヘルペスウイルスMIR1, の哺乳類相同分子の同定 (2007)
  • Author(s): 石戸聡、後藤栄治、松木洋平、星野真理、堀田博、
  • Journal Title: 第55回ウイルス学会学術集会
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] and Uematsu (2007)
  • Author(s): Ishido, S., Ohmura-Hoshino, M., Goto, E., Aoki, M., Matsuki, Y., Mito-Yoshida, M.
  • Journal Title: A novel family of membrane-bound E3 ubiquitin ligases 5th International Antigen Processing and Presentation Workshop
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Novel regulation of MHC class II function in B cells (2007)
  • Author(s): Matsuki, Y., Ohmura-Hoshino, M., Goto E., Aoki M., Mito-Yoshida M., Uematsu M., Hasegawa T., Koseki H., Ohara O., Nakayama M., Toyooka K., Matsuoka K., Hotta H., Yamamoto A., Ishido, S.
  • Journal Title: EMBO J. 26(3) Pages: 846-854
• [Journal Article] Difference in production of infectious wild-type measles and vaccine viruses in monocyte-derived dendritic cells. (2007)
  • Author(s): Ohgimoto, K., Ohgimoto, S., Ihara, T., Mizuta, H., Ishido, S., Ayata, M., Ogura, H., Hotta, H.
  • Journal Title: Virus Res. 123(1)
• [Journal Article] Difference in production of infectious wild-type measles and vaccine viruses in monocyte-derived dendritic cells. (2006)
  • Author(s): Ohgimoto, K., Ohgimoto, S., Ihara, T., Mizuta, H., Ishido, S., Ayata, M., Ogura, H., Hotta, H.
  • Journal Title: Virus Res. 123
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] A novel family of membrane-bound E3 ubiquitin ligases (2006)
  • Author(s): Ohmura-Hoshino, M., Goto, E., Matsuki, Y., Aoki, M., Mito, M., Uematsu, M., Hotta, H. and Ishido, S.
  • Journal Title: J. Biochem. 140
  • NAID: 10018842614
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Inhibition of MHC class II expression and immune responses by c-MIRI (2006)
  • Author(s): Ohmura-Hoshino, M., Matsuki, Y., Aoki, M., Goto, E., Mito, M., Uematsu, M., Kakiuchi, T., Hotta, H. and Ishido, S.
  • Journal Title: J. Immunol. 177
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] 膜結合型新規E3ユビキチンリガーゼファミリー (2006)
  • Author(s): 星野真理、後藤栄治、石戸聡
  • Journal Title: 実験医学 24
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Single-point mutations of hepatitis C virus NS3 that impair p53 interaction and anti-apoptotic activity of NS3. (2006)
  • Author(s): Tanaka, M., Nagano-Fujii, M., Deng, L., Ishido, S., Sada, K., Hotta, H.
  • Journal Title: Biochemical and Biophysical Research Communicaitons 340
  • NAID: 120000943971
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] ユビキチンとウイルス感染 (2006)
  • Author(s): 石戸聡
  • Journal Title: 医学のあゆみ別冊
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] KSHVに対する免疫応答 (2006)
  • Author(s): 石戸聡
  • Journal Title: 日本臨床
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Difference in production fo infectious wild-type measles and vaccine viruses in monocyte-derivedd denddritic cells. (2006)
  • Author(s): Ohgimoto, K., Ohgimoto, S., Ihara, T., Mizuta, H., Ishido, S., Ayata, M., Ogura, H., Hotta, H.
  • Journal Title: Virus Res. 2007 Jan ; 123(1) 7 Pages: 1-8
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Anovel family of membrane-bound E3 ubiquitin ligases (2006)
  • Author(s): Ohmura-Hoshino M., Goto, E., Matsuki, Y., Aoki, M., Mito, M., Uematsu, M., Hotta, H., Ishido, S.
  • Journal Title: J. Biochem. 140(2) Pages: 147-54
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of MHC class II expression and immune responses by c-MIR1 (2006)
  • Author(s): Ohmura- Hoshino, M., Matsuki, Y., Aoki, M., Goto, E., Mito, M., M. Uematsu, Kakiuchi, T., Hotta H. Ishido S.
  • Journal Title: J. Immunol. 177(1) Pages: 341-54
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 膜結合型新規E3ユビキチンリガーゼファミリー (2006)
  • Author(s): Ohmura-Hoshino M., Goto, E., Ishido, S.
  • Journal Title: 実験医学 Vol.24 10 Pages: 167-172
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Single-point utations of hepatitis Cvirus NS3 thatimpair p53 interaction and anti-apoptotic activity of NS3. (2006)
  • Author(s): Tanaka M, Nagano-Fujii M, Deng l, Ishido S, Sada K, Hotta H.
  • Journal Title: Biochemical and Biophysical Research Communicaitons 340(3) Pages: 792-799
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] ユビキチントウイルス感染 (2006)
  • Author(s): Ishido, S.
  • Journal Title: 医学のあゆみ 別册 Pages: 108-113
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] KSHV に対する免疫応答 (2006)
  • Author(s): Ishido, S.
  • Journal Title: 日本臨床 Pages: 568-575
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A novel family of membrane-bound E3 ubiquitin ligases. (2006)
  • Author(s): Ohmura-Hoshino, M., Goto, E., Matsuki, Y., Aoki, M., Mito, M., Uematsu, M., Hotta, H., Ishido,S.
  • Journal Title: J.Biochem. 140(2) Pages: 147-54
  • NAID: 10018842614
• [Journal Article] A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics. (2006)
  • Author(s): Yonashiro, R., Ishido, S., Kyo, S., Fukuda, T., Goto, E., Matsuki, Y., Ohmura-Hoshino, M., Sada, K., Hotta, H., Yamamura, H., Inatome, R., Yanagi,S.
  • Journal Title: EMBO J. 25(15): Pages: 3618-26
• [Journal Article] Inhibition of MHC class II expression and immune responses by c-MIR1 (2006)
  • Author(s): Ohmura-Hoshino, M., Matsuki, Y., Aoki, M., Goto, E., Mito, M., M.Uematsu, Kakiuchi, T., Hotta, H., Ishido,S.
  • Journal Title: J.Immunol 177(1) Pages: 341-54
• [Journal Article] Non-structural protein 4A of Hepatitis C virus accumulates on mitochondria and renders the cells prone to undergoing mitochondria-mediated apoptosis. (2006)
  • Author(s): Nomura-Takigawa, Y., Nagano-Fujii, M., Deng, L., Kitazawa, S., Ishido, S., Sada, K., Hotta,H.
  • Journal Title: J Gen Virol. 87(Pt 7): Pages: 1935-45
• [Journal Article] c-MIR functions as a potent immune suppressor (2005)
  • Author(s): Ohmura-Hoshino, M., Matsuki, Y., Goto, E., Mito, M., Aoki, M., Uematsu, M., Ishido, S.
  • Journal Title: 第35回日本免疫学会総会・学術集会
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] カポジ肉腫関連ヘルペスウイルスK3/MIR1 による免疫回避機構の解析 (2005)
  • Author(s): 後藤栄治、水戸麻理、青木雅美、植松未香、松木洋平、星野真理、堀田博、石戸聡、
  • Journal Title: 第35回日本ウイリス学会学術集会
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 主要組織適合抗原の新たな制御分子群 (2007)
  • Author(s): 後藤栄治、星野真理、松木洋平、水戸麻理、青木雅美、植松未香、石戸聡
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学学会合同大会(BMB2007)
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-15
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 主要組織適合抗原の新たな制御分子群 (2007)
  • Author(s): 後藤 栄治
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学学会合同大会(BMB2007)
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2007-12-15
• [Presentation] New players for regulation of MHC function (2007)
  • Author(s): Ishido, S., Ohmura-Hoshino, M., Goto,E., Matsuki, Y., Aoki, M., Mito-Yoshida, M., and Uematsu, M.
  • Organizer: International Symposium on Membrane Traffic
  • Place of Presentation: 淡路島
  • Year and Date: 2007-11-28
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] New players for regulation of MHC function (2007)
  • Author(s): 石戸 聡
  • Organizer: International Symposium on Membrane Traffic
  • Place of Presentation: 淡路夢舞台国際会議場(淡路島)
  • Year and Date: 2007-11-28
• [Presentation] 樹状細胞の分化に重要な役割を持つMARCH-I分子 (2007)
  • Author(s): 星野真理、松木洋平、後藤栄治、水戸麻理、青木雅美、植松未香、石戸聡
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 樹状細胞の分化に重要な役割を持つMARCH-I分子 (2007)
  • Author(s): 星野 真理
  • Organizer: 日本免疫学会総会
  • Place of Presentation: グランドプリンスホテル新高輪(品川区)
  • Year and Date: 2007-11-21
• [Presentation] カポジ肉腫関連ヘルペスウイルスMIR1,2の哺乳類相同分子の同定 (2007)
  • Author(s): 石戸聡、後藤栄治、松木洋平、星野真理、堀田博
  • Organizer: 第55回ウイルス学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2007-10-22
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] カポジ肉腫関連ヘルペスウイルスMIR1,2の哺乳類相同分子の同定 (2007)
  • Author(s): 石戸 聡
  • Organizer: 第55回ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター(札幌市)
  • Year and Date: 2007-10-22
• [Presentation] A novel family of membrane-bound E3 ubiquitin ligases (2007)
  • Author(s): Ishido, S., Ohmura-Hoshino, M., Goto, E., Aoki, M., Matsuki, T., Mito-Yoshida, M., and Uematsu, M.
  • Organizer: 5th International Antigen Processing and Presentation Workshop
  • Place of Presentation: Dunk Island
  • Year and Date: 2007-10-07
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] A novel family of membrane-bound E3 ubiquitin ligases (2007)
  • Author(s): 石戸 聡
  • Organizer: 5^<th>International Antigen Processing and Presentation Workshop
  • Place of Presentation: Dunk Island Australia
  • Year and Date: 2007-10-07
• [Patent(Industrial Property Rights)] c-MIRを利用したCD40の発現調節、及びそのスクリーニング方法 (2007)
  • Inventor(s): 石戸 聡,上坂 等
  • Industrial Property Rights Holder: 独立行政法人理化学研究所
  • Filing Date: 2007-06-01
  • Description: 「研究成果報告書概要(和文)」より
• [Patent(Industrial Property Rights)] c-MIRを機能評価できる細胞株 (2007)
  • Inventor(s): 石戸聡
  • Industrial Property Rights Holder: 独立行政法人理化学研究所
  • Filing Date: 2007-05-15
  • Description: 「研究成果報告書概要(和文)」より
• [Patent(Industrial Property Rights)] c-MIRを機能評価できる細胞株 (2007)
  • Inventor(s): 石戸 聡 後藤 栄治 水戸 麻理
  • Industrial Property Rights Holder: 理化学研究所
  • Filing Date: 2007-05-15
• [Patent(Industrial Property Rights)] c-MIRを利用したCD40の発現調節、及びそのスクリーニング方法 (2007)
  • Inventor(s): 石戸 聡 上坂 等
  • Industrial Property Rights Holder: 理化学研究所
  • Filing Date: 2007-06-01