Noncanonical NF-κB Activation by the Oncoprotein Tio Occurs Through a Nonconserved TRAF3-Binding Motif
| Autor: | Heinrich Sticht, Brigitte Biesinger, Sarah Jill de Jong, Jens-Christian Albrecht, Fabian Giehler, Arnd Kieser |
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| Rok vydání: | 2013 |
| Předmět: |
TRAF3
Rhadinovirus TNF Receptor-Associated Factor 3 Amino Acid Motifs NF-kappa B Ubiquitination Oncogene Proteins Viral Cell Biology Biology Biochemistry Molecular biology Cell biology Jurkat Cells Crosstalk (biology) Cytosol Gene Expression Regulation Humans Tumor necrosis factor alpha Signal transduction Sequence motif Molecular Biology Transcription factor Gene Cell Line Transformed Signal Transduction |
| Zdroj: | Science Signaling. 6 |
| ISSN: | 1937-9145 1945-0877 |
| DOI: | 10.1126/scisignal.2003309 |
| Popis: | Members of the nuclear factor κB (NF-κB) family of transcription factors regulate many cellular functions. Activation of NF-κB signaling is commonly classified as occurring through canonical or noncanonical pathways. Most NF-κB-inducing stimuli, including the viral oncoprotein Tio, lead to a concerted activation of both NF-κB 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-κB 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-κB cascade. Furthermore, the Tio-TRAF3 interaction did not affect components of the canonical NF-κB signaling pathway or the expression of target genes; thus, Tio induced noncanonical NF-κB independently of crosstalk with the canonical pathway. Together, these data identify a distinct molecular mechanism of noncanonical NF-κB activation that should enable studies into the particular functions of this pathway. |
| Databáze: | OpenAIRE |
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