SCFβ‐TrCP ubiquitin ligase‐mediated processing of NF‐κB p 105 requires phosphorylation of its C‐terminus by IκB kinase

摘要: Processing of the p105 precursor to form active subunit p50 NF-κB transcription factor is a unique case in which ubiquitin system involved limited processing rather than complete destruction target substrate. A glycine-rich region along with downstream acidic domain have been demonstrated be essential for processing. Here we demonstrate that following IκB kinase (IκK)-mediated phosphorylation, C-terminal (residues 918–934) serves as recognition motif SCFβ-TrCP ligase. Expression IκKβ dramatically increases wild-type p105, but not p105-Δ918–934. Dominant-negative β-TrCP inhibits IκK-dependent Furthermore, ligase and p105-Δ918–934 associate physically phosphorylation. In vitro, specifically conjugates promotes phosphorylated p105. Importantly, TrCP different from described IκBs, β-catenin human immunodeficiency virus type 1 Vpu. Since also conjugated processed, it appears can recognized under physiological conditions by two ligases, targeting distinct motifs.