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.