Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

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

RESEARCH ARTICLES

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).

Read the Full Text



To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882