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

Noncanonical NF-{kappa}B Activation by the Oncoprotein Tio Occurs Through a Nonconserved TRAF3-Binding Motif

Sarah Jill de Jong1*, Jens-Christian Albrecht1, Fabian Giehler2, Arnd Kieser2, Heinrich Sticht3, and Brigitte Biesinger1{dagger}

1 Institut für Klinische und Molekulare Virologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany.
2 Abteilung Genvektoren, Helmholtz Zentrum München–Deutsches Forschungszentrum für Gesundheit und Umwelt, D-81377 München, Germany.
3 Institutfür Biochemie, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany.

* Present address: St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY 10065, USA.

Abstract: Members of the nuclear factor {kappa}B (NF-{kappa}B) family of transcription factors regulate many cellular functions. Activation of NF-{kappa}B signaling is commonly classified as occurring through canonical or noncanonical pathways. Most NF-{kappa}B–inducing stimuli, including the viral oncoprotein Tio, lead to a concerted activation of both NF-{kappa}B pathways; however, extensive crosstalk at multiple levels between these signaling cascades restricts the ability to discriminate between the canonical and the noncanonical effects. We showed that noncanonical NF-{kappa}B activation by Tio depends on a distinct sequence motif that directly recruits tumor necrosis factor receptor–associated factor 3 (TRAF3). Through its TRAF3-binding motif, Tio triggered a ubiquitin-independent depletion of TRAF3 from the cytosol, which prevented TRAF3 from inhibiting signaling through the noncanonical NF-{kappa}B cascade. Furthermore, the Tio-TRAF3 interaction did not affect components of the canonical NF-{kappa}B signaling pathway or the expression of target genes; thus, Tio induced noncanonical NF-{kappa}B independently of crosstalk with the canonical pathway. Together, these data identify a distinct molecular mechanism of noncanonical NF-{kappa}B activation that should enable studies into the particular functions of this pathway.

{dagger} Corresponding author. E-mail: Brigitte.Biesinger{at}viro.med.uni-erlangen.de

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