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Sci. Signal., 23 April 2013
Vol. 6, Issue 272, p. ra27
[DOI: 10.1126/scisignal.2003309]


Editor's Summary

Preventing NF-{kappa}B Pathway Crosstalk
The transcription factor NF-{kappa}B (nuclear factor {kappa}B) can be activated by so-called canonical and noncanonical pathways. Activation of the noncanonical NF-{kappa}B pathway blocks the constitutive degradation of the kinase NIK (NF-{kappa}B–inducing kinase), which leads to the generation of an NF-{kappa}B subunit required for target gene expression. The viral oncoprotein Tio mimics a constitutively active receptor upstream of NF-{kappa}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-{kappa}B signaling. This TRAF3-binding motif enabled Tio to specifically activate noncanonical NF-{kappa}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-{kappa}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-{kappa}B Activation by the Oncoprotein Tio Occurs Through a Nonconserved TRAF3-Binding Motif. Sci. Signal. 6, ra27 (2013).

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