Noncanonical NF-?B activation by the oncoprotein Tio occurs through a nonconserved TRAF3-binding motif

de Jong SJ, Albrecht JC, Giehler F, Kieser A, Sticht H, Biesinger B (2013)

Publication Type: Journal article

Publication year: 2013

Journal

Science Signaling American Association for the Advancement of Science

Book Volume: 6

Pages Range: ra27

Journal Issue: 272

DOI: 10.1126/scisignal.2003309

Abstract

Members of the nuclear factor ?B (NF-?B) family of transcription factors regulate many cellular functions. Activation of NF-?B signaling is commonly classified as occurring through canonical or noncanonical pathways. Most NF-?B-inducing stimuli, including the viral oncoprotein Tio, lead to a concerted activation of both NF-?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-?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-?B cascade. Furthermore, the Tio-TRAF3 interaction did not affect components of the canonical NF-?B signaling pathway or the expression of target genes; thus, Tio induced noncanonical NF-?B independently of crosstalk with the canonical pathway. Together, these data identify a distinct molecular mechanism of noncanonical NF-?B activation that should enable studies into the particular functions of this pathway.

Authors with CRIS profile

Sarah Jill de Jong Graduiertenzentrum der FAU Heinrich Sticht Professur für Bioinformatik Brigitte Biesinger-Zwosta Institute of Clinical and Molecular Virology

Involved external institutions

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE)

How to cite

APA:

de Jong, S.J., Albrecht, J.-C., Giehler, F., Kieser, A., Sticht, H., & Biesinger, B. (2013). Noncanonical NF-?B activation by the oncoprotein Tio occurs through a nonconserved TRAF3-binding motif. Science Signaling, 6(272), ra27. https://doi.org/10.1126/scisignal.2003309

MLA:

de Jong, Sarah Jill, et al. "Noncanonical NF-?B activation by the oncoprotein Tio occurs through a nonconserved TRAF3-binding motif." Science Signaling 6.272 (2013): ra27.

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