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.