Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Cycle Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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DNA-Binding Proteins / metabolism*
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Drosophila Proteins*
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Humans
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Insect Proteins / genetics
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Ligases / metabolism*
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Molecular Sequence Data
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / metabolism
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Peptide Synthases / metabolism*
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Phosphorylation
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Protein Binding
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Protein Processing, Post-Translational
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SKP Cullin F-Box Protein Ligases
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Sequence Homology, Amino Acid
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Trans-Activators*
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Transcriptional Activation
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Ubiquitin-Protein Ligases
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beta Catenin
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beta-Transducin Repeat-Containing Proteins*
Substances
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CTNNB1 protein, human
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Carrier Proteins
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Cell Cycle Proteins
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Drosophila Proteins
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FBXW11 protein, human
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Insect Proteins
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NF-kappa B
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Trans-Activators
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beta Catenin
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beta-Transducin Repeat-Containing Proteins
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slmb protein, Drosophila
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SKP Cullin F-Box Protein Ligases
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Ubiquitin-Protein Ligases
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Ligases
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Peptide Synthases