Tom1 (target of Myb 1) is a novel negative regulator of interleukin-1- and tumor necrosis factor-induced signaling pathways.
The Tom1 (target of Myb 1) protein has VHS and GAT domains in N-terminal and central parts, respectively. The VHS domain has been found in a number of proteins, some of which have been implicated in intracellular trafficking and sorting. We previously showed that Tom1 forms a complex with Tollip, which has been reported to function in interleukin-1 (IL-1)-dependent signaling. In this study, we carried out a reporter gene assay to investigate the function of Tom1 in inflammatory cytokine-dependent signaling. It was found that overexpression of Tom1 suppresses activation of transcription factors, NF-kappaB and AP-1, induced by either IL-1beta or tumor necrosis factor (TNF)-alpha and that the VHS domain of Tom1 is indispensable for its suppressive activity. Thus, we propose that Tom1 is a common negative regulator of the signaling pathways induced by IL-1beta and TNF-alpha.
Yamakami
Megumi
M
Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Yokosawa
Hideyoshi
H
D002460:Cell Line; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B / Q000378:metabolism; D011506:Proteins / Q000502:physiology*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology
D007375:Interleukin-1; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D011506:Proteins; C120296:TOM1 protein, human; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha