Functional analysis of atypical nuclear small GTP-binding protein

• Project/Area Number: 20770103
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: TAGO Kenji Nara Institute of Science and Technology, バイオサイエンス研究科, 助教 (20306111)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 細胞情報伝達機構 / シグナル伝達 / 細胞・組織 / 蛋白質 / がん / 癌

Research Abstract

We found that κB-Ras is a novel type of nuclear-cytoplasmic small GTPase that mainly binds to GTP, and its localization seemed to be regulated by its GTP/GDP-binding state. Unexpectedly, the GDP-binding form of κB-Ras mutant exhibited a more potent inhibitory effect on NF-κB activation, and this inhibitory effect seemed to be due to suppression of the transactivation of a p65/RelA NF-κB subunit.

Research Products

• [Journal Article] Ric-8B stabilizes the alpha subunit of stimulatory G protein by inhibiting its ubiquitination. (2010)
  • Author(s): Nagai Y, Nishimura A, Tago K, Mizuno N, Itoh H.
  • Journal Title: J Biol Chem. 285(15) Pages: 11114-11120
  • Peer Reviewed
• [Journal Article] Ric-8B stabilizes the alpha subunit of stimulatory G protein by inhibiting its ubiquitination. (2010)
  • Author(s): Nagai Y
  • Journal Title: J Biol Chem. 285(15) Pages: 11114-11120
  • Peer Reviewed
• [Journal Article] Licochalcone A potently inhibits TNF・-induced NF-κB activation through the direct inhibition of IKK activation. (2009)
  • Author(s): Funakoshi-Tago M, Tanabe S, Tago K, Itoh H, Mashino T, Sonoda Y, Kasahara T.
  • Journal Title: Mol Pharmacol. 76(4) Pages: 745-53
  • Peer Reviewed
• [Journal Article] The polycythemia vera-associated Jak2 V617F mutant induces tumorigenesis in nude mice. (2009)
  • Author(s): Abe M, Funakoshi-Tago M, Tago K, Kamishimoto J, Aizu-Yokota E, Sonoda Y, Kasahara T.
  • Journal Title: Int Immunopharmacol. 9(7-8) Pages: 870-7
  • Peer Reviewed
• [Journal Article] G-protein signalling negatively regulates the stability of aryl hydrocarbon receptor. (2009)
  • Author(s): Nakata A, Urano D, Fujii-Kuriyama Y, Mizuno N, Tago K, Itoh H.
  • Journal Title: EMBO Rep. 10(6) Pages: 622-8
  • Peer Reviewed
• [Journal Article] The acute lymphoblastic leukemia-associated JAK2 L611S mutant induces tumorigenesis in nude mice. (2009)
  • Author(s): Funakoshi-Tago M, Tago K, Sumi K, Abe M, Aizu-Yokota E, Oshio T, Sonoda Y, Kasahara T.
  • Journal Title: J Biol Chem. 284(19) Pages: 12680-90
  • Peer Reviewed
• [Journal Article] Licochalcone A significantly suppresses LPS signaling pathway through the inhibition of NF-κB p65 phosphorylation at serine 276. (2009)
  • Author(s): Furusawa J, Funakoshi-Tago M, Tago K, Mashino T, Inoue H, Sonoda Y, Kasahara T.
  • Journal Title: Cell Signal. 21(5) Pages: 778-85
  • Peer Reviewed
• [Journal Article] TRAF6 negatively regulates TNF・-induced NF-κB activation. (2009)
  • Author(s): Funakoshi-Tago M, Kamada N, Shimizu T, Hashiguchi Y, Tago K, Sonoda Y, Kasahara T.
  • Journal Title: Cytokine. 45(2) Pages: 72-9
  • Peer Reviewed
• [Journal Article] G-protein signaling negatively regulates the stability of aryl hydrocarbon receptor. (2009)
  • Author(s): Nakata A
  • Journal Title: EMBO Rep. 10(6) Pages: 622-628
  • Peer Reviewed
• [Journal Article] Licochalcone A potently inhibits TNFα-induced NF-κB activation through the direct inhibition of IKK activation. (2009)
  • Author(s): Funakoshi-Tago M
  • Journal Title: Mol Pharmacol. 285(8) Pages: 5296-5307
  • Peer Reviewed
• [Journal Article] G-protein signaling negatively regulates the stability of aryl hydrocarbon receptor (2009)
  • Author(s): Nakata A
  • Journal Title: EMBO Rep(発表予定) (未定)
  • Peer Reviewed
• [Journal Article] icochalcone A is a potent inhibitor of TEL-Jak2-mediated transformation through the specific inhibition of Stat3 activation. (2008)
  • Author(s): Funakoshi-Tago M, Tago K, Nishizawa C, Takahashi K, Mashino T, Iwata S, Inoue H, Sonoda Y, Kasahara T.
  • Journal Title: Biochem Pharmacol. 76(12) Pages: 1681-93
  • Peer Reviewed
• [Journal Article] Negative regulation of Jak2 by its auto-phosphorylation at tyrosine 913 via the Epo signaling pathway. (2008)
  • Author(s): Funakoshi-Tago M, Tago K, Kasahara T, Parganas E
  • Journal Title: Ihle JN. Cell Signal. 20(11) Pages: 1995-2001
  • Peer Reviewed
• [Journal Article] Celecoxib potently inhibits TNF・-induced nuclear translocation and activation of NF-κB (2008)
  • Author(s): Funakoshi-Tago M, Shimizu T, Tago K, Nakamura M, Itoh H, Sonoda Y, Kasahara T.
  • Journal Title: Biochem Pharmacol. 76(5) Pages: 662-71
  • Peer Reviewed
• [Journal Article] TRAF6 is a critical signal transducer in IL-33 signaling pathway. (2008)
  • Author(s): Funakoshi-Tago M, Tago K, Hayakawa M, Tominaga S, Ohshio T, Sonoda Y, Kasahara T.
  • Journal Title: Cell Signal. 20(9) Pages: 1679-86
  • Peer Reviewed
• [Journal Article] Domain-domain interaction of P-Rex1 is essential for the activation and inhibition by G protein bg subunits and PKA. (2008)
  • Author(s): Urano D, Nakata A, Mizuno N, Tago K, Itoh H.
  • Journal Title: Cell Signal. 20(8) Pages: 1545-54
  • Peer Reviewed
• [Journal Article] Domain-domain interaction, of P-Rexl is essential for the activation and inhibition by G protein betagamma subunits and PKA (2008)
  • Author(s): Urano D
  • Journal Title: Cell Signal 20(8) Pages: 1545-54
  • Peer Reviewed
• [Journal Article] Orphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a G alpha 12/13 and Rho pathway. (2008)
  • Author(s): Iguchi T
  • Journal Title: J Biol Chem 283 (21) Pages: 14469-78
  • Peer Reviewed
• [Presentation] Structural basis of a novel targeting site for the specific inhibition of heterotrimeric G proteins (2009)
  • Author(s): 西村明幸
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 神奈川
• [Presentation] Gタンパク質シグナルによるdoublecortinのリン酸化と細胞遊走の解析 (2009)
  • Author(s): 吉田真奈美
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 兵庫
• [Presentation] 三量体Gタンパク質G・sのユビキチン化はRic-8Bとの結合により抑制される (2009)
  • Author(s): 永井裕介
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 兵庫
• [Presentation] Ric-8B accelerates Gs signaling through the stabilization of the a subunit of stimulatory G protein (2009)
  • Author(s): 永井裕介
  • Organizer: The American Society for Cell Biology 49th annualmeeting
  • Place of Presentation: 米国San Diego, CA
• [Presentation] NF-κB活性化に対する低分子量GTP結合タンパク質κB-Rasの抑制機構あ解析 (2008)
  • Author(s): 向縄昌輝
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] NF-κBシグナルに対する哺乳動物の2種類のRic-8の作用 (2008)
  • Author(s): 加戸美奈
  • Organizer: 31回日本分子生物学会年会、第81回日本生化学会大会合同大会
  • Place of Presentation: 兵庫
• [Presentation] NF-κB活性化に対する低分子量GTP結合タンパク質κB-Rasの抑制機構の解析 (2008)
  • Author(s): 向縄昌輝
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会大会合同大会
  • Place of Presentation: 兵庫