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

2013 Fiscal Year Final Research Report

• 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
• Keywords: NF-kappaB / TCR

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) Pages: e85762
• [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
• [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
  • Year and Date: 20131011-13
• [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
  • Year and Date: 20111014-16