A novel signal transduction pathway which regulates the structure of P-body and the dynamics of ARE-mRNAs

• Project/Area Number: 22659015
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: KATADA Toshiaki 東京大学, 大学院・薬学系研究科, 教授 (10088859)
• Co-Investigator(Kenkyū-buntansha): KAJIHO Hiroaki 東京大学, 大学院・薬学系研究科, 助教 (70401221)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,000,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: シグナル伝達 / G蛋白質 / P-body / mRNA動態 / Gサイクル / ゲノムプロジェクト / Processing body

Research Abstract

Processing bodies(P-bodies) contain a common set of conserved RNA-processing enzymes, and mRNAs with AU-rich elements(AREs) are delivered to P-bodies for translational silencing. It is unclear how small GTPases are involved in the P-body regulation and the ARE-mRNA metabolism. We found here that overexpression of the RhoA-subfamily GTPases alters the P-body dynamics in HeLa cells. Interestingly, both RhoA activation and glucose depletion inhibit the mRNA accumulation and degradation. These findings indicate that RhoA participates in the stress-induced rearrangement of P-bodies and the release of nucleated ARE-mRNAs for their stabilization.

Research Products

• [Journal Article] RINL, guanine nucleotide exchange factor Rab5-subfamily, is involved in the EphA8-degradation pathway with odin (2012)
  • Author(s): Kajiho H, Fukushima S, Kontani K, Katada T.
  • Journal Title: Plo S One Volume: 7(1)
  • Peer Reviewed
• [Journal Article] A novel acetylation cycle of the transcription co-activator Yes-associated protein that is downstream of the Hippo pathway is triggered in response to SN2 alkylating agents (2012)
  • Author(s): Hata S, Hirayama J, Kajiho H, Nakagawa K, Hata Y, Katada T, Furutani-Seiki M, Nishina H.
  • Journal Title: J. Biol. Chem Volume: (in press)
  • Peer Reviewed
• [Journal Article] Stress-activated protein kinase MKK7 regulates axon elongation in the developing cerebral cortex (2011)
  • Author(s): Yamasaki T, Kawasaki H, Arakawa S, Shimizu K, Shimizu S, Reiner O, Okano H, Nishina S, Azuma N, Penninger JM, Katada T, Nishina H.
  • Journal Title: J Neurosci Volume: 31 Pages: 16872-16883
  • Peer Reviewed
• [Journal Article] Characterization of RIN3 as a guanine-nucleotide exchange factor for the Rab5-subfamily GTPase Rab31 (2011)
  • Author(s): Kajiho H, Sakurai, K, Minoda T, Yoshikawa M, Nakagawa S, Fukushima S, Kontani K, Katada T.
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 24364-24373
  • Peer Reviewed
• [Journal Article] cTAGE5 mediates collagen secretion through interaction with TANGO1 at endoplasmic reticulum exit sites (2011)
  • Author(s): Saito K, Yamashiro K, Ichikawa Y, Erlmann P, Kontani K, Malhotra V, Katada T.
  • Journal Title: Mol. Biol. Cell Volume: 22 Pages: 2301-2308
  • Peer Reviewed
• [Journal Article] RASSF7 negatively regulates pro-apoptotic JNK signaling by inhibiting the activity of hosphorylated-MKK7 (2011)
  • Author(s): Takahashi S, Ebihara A, Kajiho H, Kontani K, Nishina H, Katada T.
  • Journal Title: Cell Death Differ Volume: 18 Pages: 645-655
  • Peer Reviewed
• [Journal Article] RhoA activation participates in rearrangement of processing bodies and release of nucleated AU-rich mRNAs (2011)
  • Author(s): Takahashi S, Sakurai K, Ebihara A, Kajiho H, Saito K, Kontani K, Nishina H, Katada T.
  • Journal Title: Nucleic Acids Res Volume: 39 Pages: 3446-3457
  • Peer Reviewed
• [Journal Article] RhoA activation participates in rearrangement of processing bodies and release of nucleated AU-rich mRNAs (2011)
  • Author(s): Takahashi, S., Sakurai, K., Ebihara, A., Kajiho, H., Saito, K., Kontani, K., Nishina, H., and Katada, T.
  • Journal Title: Nucleic Acids Res Volume: 39 Issue: 8 Pages: 3446-3457
  • DOI: 10.1093/nar/gkq1302
  • Peer Reviewed
• [Journal Article] RASSF7 negatively regulates pro-apoptotic JNK signaling by inhibiting the activity of phosphorylated-MKK7 (2011)
  • Author(s): Takahashi, S., Ebihara, A., Kajiho, H., Kontani, K., Nishina, H., and Katada, T.
  • Journal Title: Cell Death Differ Volume: 18 Issue: 4 Pages: 645-655
  • DOI: 10.1038/cdd.2010.137
  • Peer Reviewed
• [Journal Article] RhoA activation participates in rearrangement of processing bodies and release of nucleated AU-rich mRNAS. (2011)
  • Author(s): Takahashi s, et. al.
  • Journal Title: Nucleic Acids Res. Volume: 39(in press)(掲載確定)
  • Peer Reviewed
• [Journal Article] The Arf-like GTPase Arl8 mediates delivery of ndocytosed macromolecules to lysosomes in Caenorhabditis elegans (2010)
  • Author(s): Nakae I, Fujino T, Kobayashi T, Sasaki A, Kikko Y, Fukuyama M, Gengyo-Ando K, Mitani S, Kontani K, Katada T.
  • Journal Title: Mol. Biol. Cell Volume: 21 Pages: 2434-2442
  • Peer Reviewed
• [Journal Article] Joubert syndrome Arl13b functions at ciliary membranes and stabilizes protein transport in Caenorhabditis elegans (2010)
  • Author(s): Cevik S, Hori Y, Kaplan OI, Kida K, Toivenon T, Foley-Fisher C, Cottell D, Katada T, Kontani K, Blacque OE.
  • Journal Title: J. Cell Biol Volume: 188 Pages: 953-969
  • Peer Reviewed
• [Journal Article] Quantitative characterization of Tob interactions provides the thermodynamic basis for translation termination-coupled deadenylase regulation (2010)
  • Author(s): Ruan L, Osawa M, Hosoda N, Imai S, Machiyama A, Katada T, Hoshino S, Shimada I.
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 27624-27631
  • Peer Reviewed
• [Journal Article] AnArf-like small G protein, ARL-8, promotes the axonal transport of presynaptic cargoes by suppressing vesicle aggregation (2010)
  • Author(s): Klassen MP, Wu YE, Maeder CI, Nakae I, Cueva JG, Lehrman EK, Tada M, Gengyo-Ando K, Wang GJ, Goodman M, Mitani S, Kontani K, Katada T, Shen K.
  • Journal Title: Neuron Volume: 66 Pages: 710-723
  • Peer Reviewed
• [Journal Article] Gタンパク質研究の動向 (2010)
  • Author(s): 堅田利明
  • Journal Title: 細胞(The Cell) Volume: 42(3) Pages: 90-91
• [Journal Article] アミノ酸シグナル伝達に介在するGタンパク質Rag (2010)
  • Author(s): 春日秀文、福山征光、紺谷圏二、堅田利明
  • Journal Title: 細胞(The Cell) Volume: 42(3) Pages: 108-111
• [Presentation] 分子スイッチとしてのGTP結合蛋白質(特別講演) (2012)
  • Author(s): 堅田利明
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-02-07
• [Presentation] 百日咳毒素の作用機構からG蛋白質を見出した背景. (2011)
  • Author(s): 堅田利明
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-22
• [Presentation] 細胞のシグナル伝達系に介在するG蛋白質 (2011)
  • Author(s): 堅田利明
  • Organizer: 第77回日本生化学会東北支部例会
  • Place of Presentation: 仙台
  • Year and Date: 2011-07-23
• [Presentation] 細胞のシグナル伝達系に介在するGタンパク質: Giの発見から、Gタンパク質が果たす役割の拡大に向けて (2010)
  • Author(s): 堅田利明
  • Organizer: 特別講義
  • Place of Presentation: 東京医科歯科大学
  • Year and Date: 2010-10-08
• [Presentation] 細胞のシグナル伝達系に介在するGTP結合性制御蛋白質(G蛋白質) (2010)
  • Author(s): 堅田利明
  • Organizer: 特別講義
  • Place of Presentation: 大阪大学・医学部
  • Year and Date: 2010-05-14
• [Presentation] 低分子量G蛋白質Rab5GEF RINファミリーによる小胞輸送の機構解析 (2010)
  • Author(s): 梶保博昭、池田誠一、福島槙一、堅田利明
  • Organizer: 第1回GPCM
  • Place of Presentation: 東京
  • Year and Date: 2010-03-26
• [Book] John W. Pelly生化学(インテグレーテッドシリーズ1)共訳 (2010)
  • Author(s): 堅田利明、金保安則
  • Publisher: 東京化学同人
• [Book] 細胞内情報伝達;スタンダード薬学シリーズ4生物系薬学II.細胞をミクロに理解する第2版(日本薬学会編) (2010)
  • Author(s): 堅田利明
  • Publisher: 東京化学同人
• [Book] 分子細胞生物学第6版(翻訳分担; 15、16章) (2010)
  • Author(s): 堅田利明
  • Publisher: 東京化学同人
• [Book] ストライヤー基礎生化学第1版(翻訳分担; 12、15、16章) (2010)
  • Author(s): 堅田利明
  • Publisher: 東京化学同人
• [Remarks] 研究室ホームページ
  • URL: http://www.f.u-tokyo.ac.jp/~seiri
• [Remarks]
  • URL: http://www.f.u-tokyo.ac.jp/~seiri