Molecular mechanism of TORC1 activity and function in meiosis using a model organism.

• Project/Area Number: 26440053
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Kobe University
• Principal Investigator: Nakashima Akio 神戸大学, バイオシグナル総合研究センター, 准教授 (70397818)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: TORC1 / 減数分裂 / シグナル伝達 / モデル生物 / 分裂酵母

Outline of Final Research Achievements

The Target of rapamycin complex 1 (TORC1) protein kinase plays a critical role of several cellular controls in response to environmental inputs, including nutrients. In this study, we examined the mechanism of TORC1 regulation and its functions during meiosis even under nitrogen starvation using a model organism, the fission yeast Schizosaccharomyces pombe. We showed that TORC1 activity is substantially increased when cells enter meiotic phase under nitrogen starvation and two molecules involving meiotic progression are important for the TORC1 regulation in meiosis. TORC1 was required for meiotic progression though the regulation of gene transcription. The findings obtained in this study propose a novel molecular model of the regulation and function of TORC1 in meiosis in a wide range of eukaryotic organisms.

Research Products

• [Journal Article] TORC1-Dependent Phosphorylation Targets in Fission Yeast (2017)
  • Author(s): Otsubo Yoko、Nakashima Akio、Yamamoto Masayuki、Yamashita Akira
  • Journal Title: Biomolecules Volume: 7 Issue: 3 Pages: 50-50
  • DOI: 10.3390/biom7030050
  • Peer Reviewed / Open Access
• [Journal Article] Proline dehydrogenase promotes senescence through the generation of reactive oxygen species. (2017)
  • Author(s): Nagano T, Nakashima A, Onishi K, Kawai K, Awai Y, Kinugasa M, Iwasaki T, Kikkawa U, Kamada S.
  • Journal Title: Journal of Cell Science Volume: 130 Issue: 8 Pages: 1413-1420
  • DOI: 10.1242/jcs.196469
  • NAID: 120006462307
  • Peer Reviewed / Open Access
• [Journal Article] The loss of Lam2 and Npr2-Npr3 diminishes the vacuolar localization of Gtr1-Gtr2 and disinhibits TORC1 activity in fission yeast. (2016)
  • Author(s): Ma N, Ma Y, Nakashima A, Kikkawa U, Furuyashiki T.
  • Journal Title: PLoS One Volume: 11 Issue: 5 Pages: e0156239-e0156239
  • DOI: 10.1371/journal.pone.0156239
  • Peer Reviewed / Open Access
• [Journal Article] Overexpression of eIF5 or its protein mimic 5MP perturbs eIF2 function and induces ATF4 translation through delayed re-initiation. (2016)
  • Author(s): Kozel C, Thompson B, Hustak S, Moore C, Nakashima A, Singh CR, Reid M, Cox C, Papadopoulos E, Luna RE, Anderson A, Tagami H, Hiraishi H, Slone EA, Yoshino KI, Asano M, Gillaspie S, Nietfeld J, Perchellet JP, Rothenburg S, Masai H, Wagner G, Beeser A, Kikkawa U, Fleming SD, Asano K.
  • Journal Title: Nucleic Acids Res. Volume: 44 Issue: 18 Pages: 8704-8713
  • DOI: 10.1093/nar/gkw559
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of cellular senescence-specific genes by comparative transcriptomics (2016)
  • Author(s): Nagano T, Nakano M, Nakashima A, Onishi K, Yamao S, Enari M, Kikkawa U, Kamada S
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 31758-31758
  • DOI: 10.1038/srep31758
  • NAID: 120005842606
  • Peer Reviewed / Open Access
• [Journal Article] Versatile function of the circadian protein CIPC as a regulator of Erk activation. (2016)
  • Author(s): Matsunaga R., Nishino T., Yokohama A., Nakashima A., Kikkawa U., and Konishi H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 469 Issue: 3 Pages: 377-383
  • DOI: 10.1016/j.bbrc.2015.11.117
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Midostaurin preferentially attenuates proliferation of triple-negative breast cancer cell lines through inhibition of Aurora kinase family. (2015)
  • Author(s): Kawai M., Nakashima A., Kamada S., and Kikkawa U.
  • Journal Title: J Biomed. Sci. Volume: 22 Issue: 1 Pages: 48-48
  • DOI: 10.1186/s12929-015-0150-2
  • Peer Reviewed / Open Access
• [Journal Article] Identification of Regions Critical for the Integrity of the TSC1-TSC2-TBC1D7 Complex. (2014)
  • Author(s): Santiago, Lima, A.J., Hoogeveen-Westerveld, M., Nakashima, A., Maat-Kievit, A., van den Ouweland, A., Halley, D., Kikkawa, U., and Nellist, M.
  • Journal Title: PLoS One Volume: 9 Issue: 4 Pages: e93940-e93940
  • DOI: 10.1371/journal.pone.0093940
  • Peer Reviewed / Open Access
• [Journal Article] Fission yeast arrestin-related trafficking adaptor, Arn1/Any1, is ubiquitinated by Pub1 E3 ligase and regulates endocytosis of Cat1 amino acid transporter. (2014)
  • Author(s): Nakashima, A., Kamada, S., Tamanoi, F., and Kikkawa, U.
  • Journal Title: Biol. Open Volume: 3 Issue: 6 Pages: 542-552
  • DOI: 10.1242/bio.20148367
  • NAID: 120005460282
  • Peer Reviewed / Open Access
• [Presentation] 減数分裂における分裂酵母TORC1の制御 (2017)
  • Author(s): 中嶋 昭雄
  • Organizer: ConBio2017（生命科学系学会合同年次大会）, 神戸市ポートアイランド
  • Invited
• [Presentation] フェロモン応答シグナルによる分裂酵母TORC1 制御の可能性 (2016)
  • Author(s): 中嶋昭雄，吉川 潮
  • Organizer: 第６回ＴＯＲ研究会
  • Place of Presentation: 東京大学分子細胞生物学研究所 (東京都・文京区）
  • Year and Date: 2016-09-30
• [Presentation] 減数分裂における分裂酵母TORC1の制御と機能 (2015)
  • Author(s): 中嶋 昭雄; 山下 朗; 大坪 瑶子; 鎌田 真司; 瓜谷 眞裕; 山本 正幸; 吉川 潮
  • Organizer: Biochemistry and Molecular Biology 2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県・神戸市）
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] 減数分裂における分裂酵母TORC1 の制御と機能 (2015)
  • Author(s): 中嶋 昭雄; 吉川 潮
  • Organizer: 第５回TOR研究会
  • Place of Presentation: 新潟大学脳研究所（新潟県・新潟市）
  • Year and Date: 2015-10-16
• [Presentation] Regulation of TORC1 signaling in meiosis under nitrogen starvation (2015)
  • Author(s): Nakashima Akio; Yamashita Akira; Otsubo Yoko; Kamada Shinji; Uritani Masahiro; Yamamoto Masayuki; Kikkawa Ushio
  • Organizer: THE EIGHTH INTERNATIONAL FISSION YEAST MEETING
  • Place of Presentation: Kobe, Japan（兵庫県・神戸市）
  • Year and Date: 2015-06-21
  • Int'l Joint Research
• [Presentation] プロリン脱水素酵素（PRODH）は細胞老化誘導に関わる新規因子である (2014)
  • Author(s): 長野 太輝、山尾 俊介、中嶋 昭雄、吉川 潮、鎌田 真司
  • Organizer: 第37回日本分子生物学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 新規細胞老化誘導因子としてのDアミノ酸酸化酵素DAOの機能解析 (2014)
  • Author(s): 山尾 俊介、長野 太輝、中嶋 昭雄、吉川 潮、鎌田 真司
  • Organizer: 第37回日本分子生物学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 分裂酵母 TORC1 の減数分裂における活性化と機能の検討 (2014)
  • Author(s): 中嶋 昭雄、吉川 潮
  • Organizer: 第４回TOR研究会
  • Place of Presentation: 基礎生物学研究所
  • Year and Date: 2014-09-17 – 2014-09-18
• [Presentation] 分裂酵母 TORC1 の窒素源飢餓時の再活性化と生理機能 (2014)
  • Author(s): 中嶋 昭雄、吉川 潮
  • Organizer: 第47回酵母遺伝学フォーラム報告会
  • Place of Presentation: 東京大学農学部弥生キャンパス東京大学弥生講堂
  • Year and Date: 2014-09-01 – 2014-09-02
• [Presentation] 多機能性 TORC1 キナーゼの液胞依存性栄養シグナルによる活性制御システムの解明 (2014)
  • Author(s): 中嶋 昭雄
  • Organizer: 第186回酵母細胞研究会例会平成24年度地神芳文記念研究助成金研究成果報告会
  • Place of Presentation: キリンビール（株）横浜工場
  • Year and Date: 2014-07-11
  • Invited
• [Remarks] バイオシグナル総合研究センター細胞情報研究分野
  • URL: http://www.research.kobe-u.ac.jp/brce-kikkawa/
• [Remarks] バイオシグナル総合研究センター 細胞情報研究分野
  • URL: http://www.research.kobe-u.ac.jp/brce-kikkawa/
• [Remarks] 神戸大学自然科学系先端融合研究環バイオシグナル研究センター
  • URL: http://www.biosig.kobe-u.ac.jp
• [Remarks] 神戸大学自然科学系先端融合研究環バイオシグナル研究センター細胞情報研究分野
  • URL: http://www.research.kobe-u.ac.jp/brce-kikkawa/
• [Remarks] 神戸大学自然科学系先端融合研究環バイオシグナル研究センター
  • URL: http://www.biosig.kobe-u.ac.jp/