T2BP, a novel TRAF2 binding protein, can activate NF-kappaB and AP-1 without TNF stimulation.
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.
Kanamori
Mutsumi
M
Laboratory for Genome Exploration Research Group, RIKEN Genomic Sciences Center (GSC), 1-7-22 Suehiro-cho, Yokohama, Tsurumi-ku, 230-0045, Japan.
Suzuki
Harukazu
H
Saito
Rintaro
R
Muramatsu
Masami
M
Hayashizaki
Yoshihide
Y
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
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