title: Brap2 regulates temporal control of NF-κB localization mediated by inflammatory response.
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.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Takashima
authors.forename: Fuminori
authors.initials: F
authors.lastname: Tsuruta
authors.forename: Yu
authors.initials: Y
authors.lastname: Kigoshi
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Jaehyun
authors.initials: J
authors.lastname: Kim
authors.forename: Megumi C
authors.initials: MC
authors.lastname: Katoh
authors.forename: Tomomi
authors.initials: T
authors.lastname: Fukuda
authors.forename: Kenji
authors.initials: K
authors.lastname: Irie
authors.forename: Tomoki
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D044842:Cullin Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D000075687:NEDD8 Protein; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D021381:Protein Transport / Q000187:drug effects; D016415:Sequence Alignment; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism
chemical_list: C100318:Cullin 1; D044842:Cullin Proteins; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014452:Ubiquitins; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases
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