Reseach on RNA helicase, MOV10, which negatively regulates NF-kappaB activation

• Project/Area Number: 23591383
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto University
• Principal Investigator: KOBAYASHI Masayuki 京都大学, 医学(系)研究科(研究院), 助教 (90513820)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: NF-kappaB / TCR / NF kappaB / T cell biology / T cell receptor / NFκB / T細胞

Research Abstract

Ectopic MOV10 expression clearly suppressed NF-kappaB activation in Jurkat T cells. But knock down of MOV10 in Jurkat T cells didn't affect NF-kappaB activation. Alternatively we performed a cell-based screening for negative regulators of TCR-mediated NF-kappaB activation. We found that casein kinase-2 interacting protein-1 (CKIP-1) suppresses PKCtheta-CBM-NF-kappaB signaling. We found that CKIP-1 interacts with CARMA1 and competes with PKCtheta for association. CKIP-1 represses NF-kappaB activity in unstimulated cells, and inhibits NF-kappaB activation induced by stimulation with PMA or constitutively active PKCtheta, but not by stimulation with TNFalfa. These data suggest that CKIP-1 contributes maintenance of a resting state on NF-kappaB activity or prevents T cells from being activated by inadequate signaling. In conclusion, we demonstrate that CKIP-1 interacts with CARMA1 and has an inhibitory effect on PKCtheta-CBM-NF-kappaB signaling.

Research Products

• [Journal Article] CKIP-1 is an intrinsic negative regulator of T-cell activation through an interaction with CARMA1 (2014)
  • Author(s): Takashi Sakamoto, Masayuki Kobayashi, Kohei Tada, Masanobu Shinohara, Katsuhiro Io, Kayoko Nagata, Fumie Iwai, Yoko Takiuchi, Yasuyuki Arai, Kouhei Yamashita, Keisuke Shindo, Norimitsu Kadowaki, Yoshio Koyanagi and Akifumi Takaori-Kondo
  • Journal Title: PLOS One Volume: 9(1)
• [Journal Article] Defining HIV-1 Vif residues that interact with CBF-beta by site-directed mutagenesis (2014)
  • Author(s): Matsui M, Shindo K, Nagata K, Io K, Tada K, Iwai F, Kobayashi M, Kadowaki N, Harris RS, Takaori-Kondo A
  • Journal Title: Virology Volume: 449 Pages: 82-87
• [Journal Article] CKIP-1 Is an Intrinsic Negative Regulator of T-Cell Activation through an Interaction with CARMA1. (2014)
  • Author(s): Sakamoto T, Kobayashi M, Tada K, Shinohara M, Io K, Nagata K, Iwai F, Takiuchi Y, Arai Y, Yamashita K, Shindo K, Kadowaki N, Koyanagi Y, Takaori-Kondo A
  • Journal Title: PLoS One Volume: 9 Issue: 1 Pages: 1-11
  • DOI: 10.1371/journal.pone.0085762
  • Peer Reviewed
• [Journal Article] Defining HIV-1 Vif residues that interact with CBF by site-directed mutagenesis. (2014)
  • Author(s): Matsui Y, Shindo K, Nagata K, Io K, Tada K, Iwai F, Kobayashi M, Kadowaki N, Harris R, Takaori-Kondo A
  • Journal Title: Virology Volume: 449 Pages: 82-87
  • DOI: 10.1016/j.virol.2013.11.004
  • Peer Reviewed
• [Presentation] CKIP-1 is an intrinsic negative regulator for T cell activation through interacting with CARMA1 (2013)
  • Author(s): Takashi Sakamoto, Masayuki Kobayashi, Kohei Tada, Masanobu Shinohara, Katsuhiro Io, Yasuyuki Arai, Kouhei Yamashita, Keisuke Shindo, Norimitsu Kadowaki, Yoshio Koyanagi, Akifumi Takaori-Kondo
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌
• [Presentation] Search for negative regulators in T cell receptor-mediated NFkappaB activation T細胞受容体からのNF-kappaBシグナル伝達を負に制御する新規分子の探索 (2011)
  • Author(s): Takashi Sakamoto, Masayuki Kobayashi, Kohei Tada, Yuya Nagai, Masanobu Shinohara, Katsuhiro Io, Masashi Matsui, Keisuke Shindo, Yoshio Koyanagi, Akifumi Takaori-Kondo
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] T細胞受容体からのNF-κBシグナル伝達を負に制御する新規分子の探索 (2011)
  • Author(s): 阪本貴士
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場（愛知県）
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~hemonc/