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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

Oncogene volume 18, pages 2039–2046 (1999)Cite this article

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/hβTrCP. Being a part of SCF complex with Skp1 and Cullin1, HOS specifically interacted with the phosphorylated IκB and β-catenin, targeting these proteins for proteasome-dependent degradation in vivo. This targeting required Cullin1 as expression of a mutant Cullin1 abrogated the degradation of IκB and of β-catenin. Mutant HOS which lacks the F-box blocked TNFα-induced degradation of IκB as well as GSK3β-mediated degradation of β-catenin. This mutant also inhibited NF-κB transactivation and increased the β-catenin-dependent transcription activity of Tcf. These results demonstrate that SCFHOS E3 ubiquitin ligase regulate both NF-κB and β-catenin signaling pathways.

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Acknowledgements

We thank M Karin, K Kinzler, B Vogelstein, A Chan and E Krebs for providing valuable reagents. We are grateful to V Fried, M Hochstrasser and T Buschmann for critical reading of the manuscript. The study was supported by The Incentive Mount Sinai School of Medicine Dean Award and NIH grants CA 78419 (Z Ronai) and GM 55059 (Z-Q Pan).

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Authors and Affiliations

  1. Derald H Ruttenberg Cancer Center, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, 10029-6574, NY, USA

    Serge Y Fuchs, Angus Chen, Zhen-Qiang Pan & Ze'ev Ronai

  2. Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina, 27599, NC, USA

    Yue Xiong

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  1. Serge Y Fuchs
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  2. Angus Chen
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Fuchs, S., Chen, A., Xiong, Y. et al. 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. Oncogene 18, 2039–2046 (1999). https://doi.org/10.1038/sj.onc.1202760

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