HOS, a human homolog of Slimb, forms an SCF complex with Skp1 and Cullin1 and targets the phosphorylation-dependent degradation of IκB and β-catenin

SCF E3 ubiquitin ligases mediate ubiquitination and proteasome-dependent degradation of phosphorylated substrates. We identified a human F-box/WD40 repeats protein (HOS), which is homologous to Slimb/h beta TrCP. Being a part of SCF complex with Skp1 and Cullin1, HOS specifically interacted with the phosphorylated I kappa B and beta-catenin, targeting these proteins for proteasome-dependent degradation in vivo, This targeting required Cullin1 as expression of a mutant Cullin1 abrogated the degradation of I kappa B and of beta-catenin. Mutant HOS which lacks the F-box blocked TNF alpha-induced degradation of I kappa B as well as GSK3 beta-mediated degradation of beta-catenin. This mutant also inhibited NF-kappa B transactivation and increased the beta-catenine-dependent transcription activity of Tcf. These results demonstrate that SCFHOS E3 ubiquitin ligase regulate both NF-kappa B and beta-catenin signaling pathways.