1. Brap2 regulates temporal control of NF-κB localization mediated by inflammatory response.
- Author
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Takashima O, Tsuruta F, Kigoshi Y, Nakamura S, Kim J, Katoh MC, Fukuda T, Irie K, and Chiba T
- Subjects
- Amino Acid Sequence, Cell Line, Cell Nucleus metabolism, Cullin Proteins metabolism, Humans, Models, Biological, Molecular Sequence Data, NEDD8 Protein, Protein Binding, Protein Interaction Domains and Motifs, Protein Multimerization, Protein Transport drug effects, Sequence Alignment, Tumor Necrosis Factor-alpha pharmacology, Ubiquitin-Protein Ligases chemistry, Ubiquitins metabolism, Inflammation metabolism, NF-kappa B metabolism, Ubiquitin-Protein Ligases metabolism
- Abstract
Nuclear factor-kappaB (NF-κB) is critical for the expression of multiple genes involved in inflammatory responses and cellular survival. NF-κB is normally sequestered in the cytoplasm through interaction with an inhibitor of NF-κB (IκB), but inflammatory stimulation induces proteasomal degradation of IκB, followed by NF-κB nuclear translocation. The degradation of IκB is mediated by a SCF (Skp1-Cullin1-F-box protein)-type ubiquitin ligase complex that is post-translationaly modified by a ubiquitin-like molecule Nedd8. In this study, we report that BRCA1-associated protein 2 (Brap2) is a novel Nedd8-binding protein that interacts with SCF complex, and is involved in NF-κB translocation following TNF-α stimulation. We also found a putative neddylation site in Brap2 associated with NF-κB activity. Our findings suggest that Brap2 is a novel modulator that associates with SCF complex and controls TNF-α-induced NF-κB nuclear translocation.
- Published
- 2013
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