HOS, a human homolog of Slimb, forms an SCF complex with Skp1 and Cullin1 and targets the phosphorylation-dependent degradation of IkappaB and beta-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 betaTrCP. Being a part of SCF complex with Skp1 and Cullin1, HOS specifically interacted with the phosphorylated IkappaB 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 IkappaB and of beta-catenin. Mutant HOS which lacks the F-box blocked TNF alpha-induced degradation of IkappaB as well as GSK3beta-mediated degradation of beta-catenin. This mutant also inhibited NF-kappaB transactivation and increased the beta-catenin-dependent transcription activity of Tcf. These results demonstrate that SCF(HOS) E3 ubiquitin ligase regulate both NF-kappaB and beta-catenin signaling pathways.
Mesh Terms:
Amino Acid Sequence, Carrier Proteins, Cell Cycle Proteins, Cytoskeletal Proteins, DNA-Binding Proteins, Drosophila Proteins, Humans, Insect Proteins, Ligases, Molecular Sequence Data, NF-kappa B, Peptide Synthases, Phosphorylation, Protein Binding, Protein Processing, Post-Translational, SKP Cullin F-Box Protein Ligases, Sequence Homology, Amino Acid, Trans-Activators, Transcriptional Activation, Ubiquitin-Protein Ligases, beta Catenin, beta-Transducin Repeat-Containing Proteins
Oncogene
Date: Mar. 25, 1999
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