title: NF-kappaB activator Act1 associates with IL-1/Toll pathway adaptor molecule TRAF6.
abstract: NF-kappaB activator 1 (Act1), also called CIKS, is a recently identified protein with NF-kappaB and AP-1 activation activities through its association with the IkappaB kinase complex. We identified and confirmed that Act1 interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6); notably, Act1 binds to TRAF6 only among TRAF family proteins. The amino-terminal half of Act1 is required for its interaction with the TRAF domain. Act1-mediated NF-kappaB activation was inhibited by a dominant-negative mutant of TRAF6 in a dose-dependent manner, and IL-1-induced NF-kappaB activation was inhibited by a high level of Act1 expression. Our results suggest that Act1 is involved in IL-1/Toll-mediated signaling through TRAF6.
authors.affiliation: Laboratory for Genome Exploration Research Group, RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Kanamori
authors.forename: Chikatoshi
authors.initials: C
authors.lastname: Kai
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Harukazu
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D029721:Drosophila Proteins; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6; D051193:Toll-Like Receptors; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D020798:Two-Hybrid System Techniques
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D029721:Drosophila Proteins; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011506:Proteins; D011956:Receptors, Cell Surface; D048029:TNF Receptor-Associated Factor 6; C414202:TRAF3IP2 protein, human; D051193:Toll-Like Receptors; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins