title: T2BP, a novel TRAF2 binding protein, can activate NF-kappaB and AP-1 without TNF stimulation.
abstract: TRAF2 is a key molecule involved in TNF signaling, which is crucial for the regulation of inflammatory processes. We have identified a novel TRAF2 binding protein, designated as T2BP (TRAF2 binding protein), by a mammalian two-hybrid screening approach. T2BP is a relatively small protein of 184 amino acids, which includes a forkhead-associated domain, the phosphopeptide binding motif. The interaction domain search showed that the TRAF domain in TRAF2 is required for the binding to T2BP whereas almost the entire protein in T2BP binds to TRAF2. The interaction was further confirmed by co-immunoprecipitation. Expression profiling for T2BP and TRAF2 revealed an ubiquitous expression in adult mouse tissues. Overexpression of T2BP in HEK293 cells activated NF-kappaB and AP-1 in a dose dependent manner as well as seen in the TNF-treated control cells. Our results suggest that T2BP is involved in the TNF-mediated signaling by its interaction with TRAF2.
authors.affiliation: Laboratory for Genome Exploration Research Group, RIKEN Genomic Sciences Center (GSC), 1-7-22 Suehiro-cho, Yokohama, Tsurumi-ku, 230-0045, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Kanamori
authors.forename: Harukazu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Rintaro
authors.initials: R
authors.lastname: Saito
authors.forename: Masami
authors.initials: M
authors.lastname: Muramatsu
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D002460:Cell Line; D051858:Forkhead Transcription Factors; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D047992:TNF Receptor-Associated Factor 2; D014018:Tissue Distribution; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry; D015533:Transcriptional Activation; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D020798:Two-Hybrid System Techniques
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D051858:Forkhead Transcription Factors; D016328:NF-kappa B; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; C499176:T2bp protein, mouse; C446759:TIFA protein, human; D047992:TNF Receptor-Associated Factor 2; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha