Nuclear-specific arginine methylation of glycolytic enzymes regulates energy metabolism

• Project/Area Number: 15H04355
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Keio University
• Principal Investigator: YAMAMOTO Takehiro 慶應義塾大学, 医学部(信濃町), 講師 (50383774)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000); Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
• Keywords: 解糖系 / メチル化 / PRMT1 / 核移行 / アルギニンメチル化 / メチオニン代謝

Outline of Final Research Achievements

In cancer cells, the expression of glycolytic enzymes is regulated by stress-responsive transcriptional factors (e.g., HIF-Ia and c-Myc). Recent studies demonstrated that post-translational modifications of metabolic enzymes also regulate metabolic reprogramming. Our previous study showed that arginine methylation of glycolytic enzymes is spatial regulated in the nucleus. In this study, we clarified the mechanism of nuclear-specific arginine methylation of enzymes. Furthermore, we found that auto-methylation of PRMT1, which is a responsible methyltransferase for glycolytic enzymes influenced the nuclear translocation of PRMT1, resulted in nuclear-specific methylation of glycolytic enzymes.

Research Products

• [Journal Article] Gold-nanofève surface-enhanced Raman spectroscopy visualizes hypotaurine as a robust anti-oxidant consumed in cancer survival (2018)
  • Author(s): Shiota M, Naya M, Yamamoto T, Hishiki T, Tani T, Takahashi H, Kubo A, Koike D, Itoh M, Ohmura M, Kabe Y, Sugiura Y, Hiraoka N, Morikawa T, Takubo K, Suina K, Nagashima H, Sampetrean O, Nagano O, Saya H, Yamazoe S, Watanabe H, Suematsu M
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 1561-1561
  • DOI: 10.1038/s41467-018-03899-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characterization and validation of Entamoeba histolytica pantothenate kinase as a novel anti-amebic drug target. (2018)
  • Author(s): Nurkanto A, Jeelani G, Yamamoto T, Naito Y, Hishiki T, Mori M, Suematsu M, Shiomi K, Hashimoto T, Nozaki T
  • Journal Title: Int J Parasitol Drugs Drug Resist. Volume: 8 Issue: 1 Pages: 125-136
  • DOI: 10.1016/j.ijpddr.2018.02.004
  • NAID: 120007134287
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] メチオニン代謝 -がん細胞における制御機構とその役割 (2017)
  • Author(s): 山本雄広、伊藤真衣、大津 陽、末松 誠
  • Journal Title: 実験医学増刊号 Volume: 35 Pages: 52-59
• [Journal Article] Rewiring of embryonic glucose metabolism via suppression of PFK-1 and aldolase during mouse chorioallantoic branching (2017)
  • Author(s): Miyazawa, H., Yamaguchi, Y., Sugiura, Y., Honda, K., Kondo, K., Matsuda, F., Yamamoto, T., Suematsu, M., and Miura, M
  • Journal Title: Development Volume: 144 Issue: 1 Pages: 63-73
  • DOI: 10.1242/dev.138545
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CO-CBS-H2 S Axis: From Vascular Mediator to Cancer Regulator. (2016)
  • Author(s): Suematsu M, Nakamura T, Tokumoto Y, Yamamoto T, Kajimura M, Kabe Y.
  • Journal Title: Microcirculation Volume: 23 Issue: 3 Pages: 183-190
  • DOI: 10.1111/micc.12253
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cystathionine beta-synthase and PGRMC1 as CO sensors. (2016)
  • Author(s): Kabe Y, Yamamoto T, Kajimura M, Sugiura Y, Koike I, Ohmura M, Nakamura T, Tokumoto Y, Tsugawa H, Handa H, Kobayashi T, and Suematsu M.
  • Journal Title: Free Radical Biology & Medicine Volume: 99 Pages: 333-344
  • DOI: 10.1016/j.freeradbiomed.2016.08.025
  • Peer Reviewed / Open Access
• [Journal Article] ガスシグナルを介した翻訳後修飾によるがん細胞の代謝制御 (2016)
  • Author(s): 山本雄広、末松 誠
  • Journal Title: The LUNG Volume: 24 Pages: 80-86
• [Journal Article] メチオニン代謝に起因するメチル化修飾を介した、がん細胞のエネルギー代謝制御機構 (2016)
  • Author(s): 山本雄広、末松 誠
  • Journal Title: 生化学 Volume: 88 Pages: 397-401
• [Journal Article] CO-CBS-H2 S Axis: From Vascular Mediator to Cancer Regulator. (2016)
  • Author(s): Suematsu M, Nakamura T, Tokumoto Y, Yamamoto T, Kajimura M, Kabe Y.
  • Journal Title: Microcirculation Volume: 23 Pages: 183-190
  • Peer Reviewed
• [Journal Article] nnate Response to Human Cancer Cells with or without IL-2 Receptor Common γ-Chain Function in NOD Background Mice Lacking Adaptive Immunity. (2015)
  • Author(s): Nishime C, Kawai K, Yamamoto T, Katano I, Monnai M, Goda N, Mizushima T, Suemizu H, Nakamura M, Murata M, Suematsu M, Wakui M.
  • Journal Title: J Immunol Volume: 195 Issue: 4 Pages: 1883-1890
  • DOI: 10.4049/jimmunol.1402103
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 翻訳後修飾を介した解糖系酵素PKM2の核移行メカニズムの解析 (2017)
  • Author(s): 山本雄広、伊藤真衣、高野直治、石渡恭子、倉堀智一、末松 誠
  • Organizer: 生命科学系合同学会ConBio2017
• [Presentation] アルギニンメチル化酵素PRMT1の核移行メカニズムの解明 (2016)
  • Author(s): 山本雄広、伊藤真衣、大津陽、長坂美咲、石渡恭子、高野直治、末松 誠
  • Organizer: 第39回日本分子生物学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-11-30
• [Presentation] アルギニンメチル化酵素PRMT1の細胞内局在機構の解明 (2016)
  • Author(s): 山本雄広、伊藤真衣、大津陽、石渡恭子、高野直治、末松 誠
  • Organizer: 第89回日本生化学会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-09-25
• [Presentation] メチオニン代謝に起因するがん細胞の糖代謝制御機構 (2016)
  • Author(s): 山本雄広
  • Organizer: 第３２回臨床フリーラジカル会議
  • Place of Presentation: 京都・けぶり河（京都府亀岡市）
  • Year and Date: 2016-01-29
  • Invited
• [Presentation] アルギニンメチル化を介したマクロファージの解糖系制御機構の解明 (2015)
  • Author(s): 山本雄広、伊藤真衣 、石渡恭子、高野直治、内藤善子、菱木貴子、末松 誠
  • Organizer: BMB2015
  • Place of Presentation: ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] Carbon monoxide regulates directional biotransformation of glucose via protein arginine methylation (2015)
  • Author(s): Yamamoto T, Takano N, Ishiwata K, Suematsu M
  • Organizer: 10th World Congress for Microcirculation
  • Place of Presentation: 京都国際会議場（京都府京都市）
  • Year and Date: 2015-09-25
  • Int'l Joint Research / Invited
• [Presentation] メチオニン代謝に起因するがん細胞の解糖系の制御機構 (2015)
  • Author(s): 山本雄広、高野直治、石渡恭子、伊藤真衣、末松誠
  • Organizer: 第３回がんと代謝研究会
  • Place of Presentation: 石川県立音楽堂（石川県金沢市）
  • Year and Date: 2015-07-16
  • Invited
• [Presentation] アルギニンメチル化を介したがん細胞のエネルギー代謝制御機構 (2015)
  • Author(s): 山本雄広
  • Organizer: 東北大学医学部酸素医学コアセンター特別セミナー
  • Place of Presentation: 東北大学（宮城県仙台市）
  • Year and Date: 2015-05-28
  • Invited
• [Remarks] 慶應義塾大学医学部医化学教室ホームページ
  • URL: http://www.gasbiology.com/