Sci. Signal., 23 April 2013
Preventing NF-B Pathway CrosstalkThe transcription factor NF-B (nuclear factor B) can be activated by so-called canonical and noncanonical pathways. Activation of the noncanonical NF-B pathway blocks the constitutive degradation of the kinase NIK (NF-B–inducing kinase), which leads to the generation of an NF-B subunit required for target gene expression. The viral oncoprotein Tio mimics a constitutively active receptor upstream of NF-B signaling, and de Jong et al. found that it contains a binding motif not conserved in other proteins that bind to TRAF3 (tumor necrosis factor receptor–associated factor 3), an inhibitor of noncanonical NF-B signaling. This TRAF3-binding motif enabled Tio to specifically activate noncanonical NF-B signaling without triggering crosstalk with the canonical pathway. Tio signaling did not result in TRAF3 degradation; rather, it induced the sequestration of a TRAF3-containing degradative complex from NIK to stimulate the noncanonical pathway. These data suggest that Tio might be used as a tool to examine the specific activation of genes targeted by noncanonical NF-B signaling in the context of viral transformation.
Citation: S. J. de Jong, J.-C. Albrecht, F. Giehler, A. Kieser, H. Sticht, B. Biesinger, Noncanonical NF-B Activation by the Oncoprotein Tio Occurs Through a Nonconserved TRAF3-Binding Motif. Sci. Signal. 6, ra27 (2013).
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