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Proteins containing the UBA domain are able to bind to multi-ubiquitin chains

Nature Cell Biology volume 3, pages 939–943 (2001)Cite this article

Abstract

The UBA domain is a motif found in a variety of proteins, some of which are associated with the ubiquitin–proteasome system1,2. We describe the isolation of a fission-yeast gene, mud1+, which encodes a UBA domain containing protein that is able to bind multi-ubiquitin chains. We show that the UBA domain is responsible for this activity. Two other proteins containing this motif, the fission-yeast homologues of Rad23 and Dsk2, are also shown to bind multi-ubiquitin chains via their UBA domains. These two proteins are implicated, along with the fission-yeast Pus1(S5a/Rpn10) subunit of the 26 S proteasome, in the recognition and turnover of substrates by this proteolytic complex.

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Figure 1: The UBA domain is able to bind to multi-ubiquitin.
Figure 2: Dph1 and Rhp23 interact with the proteasome.
Figure 3: Phenotypes of the single-mutant and double-mutant rhp23-null, dph1-null and pus1-null strains.
Figure 4: Characterization and non-rescue of the growth defect observed in the pus1Δrhp23Δ by the Rhp23 mutated proteins.

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References

  1. Hofmann, K. & Bucher, P. Trends Biochem. Sci. 21, 172–173 (1996).

    Article  CAS  Google Scholar 

  2. Hershko, A. & Ciechanover, A. Annu. Rev. Biochem. 67, 425–479 (1998).

    Article  CAS  Google Scholar 

  3. Voges, D., Zwickl, P. & Baumeister, W. Annu. Rev. Biochem. 68, 1015–1068 (1999).

    Article  CAS  Google Scholar 

  4. Deveraux, Q., Ustrell, V., Pickart, C. & Rechsteiner, M. J. Biol. Chem. 269, 7059–7061 (1994).

    CAS  PubMed  Google Scholar 

  5. Van Nocker, S., Deveraux, Q., Rechsteiner, M. & Vierstra, R. D. Proc. Natl Acad. Sci. USA 93, 856–860 (1996).

    Article  CAS  Google Scholar 

  6. Haracska, L. & Udvardy, A. Eur. J. Biochem. 231, 720–725 (1995).

    Article  CAS  Google Scholar 

  7. Van Nocker, S., et al. Mol. Cell. Biol. 16, 6020–6028 (1996).

    Article  CAS  Google Scholar 

  8. Wilkinson, C. R. M. et al. J. Biol. Chem. 275, 15182–15192 (2000).

    Article  CAS  Google Scholar 

  9. Wilkinson, C. R. M., Wallace, M., Seeger, M., Dubiel, W. & Gordon, C. J. Biol. Chem. 272, 25768–25777 (1997).

    Article  CAS  Google Scholar 

  10. Schauber, C. et al. Nature 391, 715–718 (1998).

    Article  CAS  Google Scholar 

  11. Lombaerts, M., Goeloe, J. I., den Dulk, H., Brandsma, J. A. & Brouwer, J. Biochem. Biophys. Res. Commun. 268, 210–215 (2000).

    Article  CAS  Google Scholar 

  12. Biggins, S., Ivanovska, I. & Rose, M. D. J. Cell Biol. 133, 1331–1346 (1996).

    Article  CAS  Google Scholar 

  13. He, X., Jones, M. H., Winey, M. & Sazer, S. J. Cell Sci. 111, 1635–1647 (1998).

    CAS  PubMed  Google Scholar 

  14. Bertolaet, B. L. et al. Nature Struct. Biol. 8, 417–422 (2001).

    Article  CAS  Google Scholar 

  15. Sambrook, J. & Russell, D. Molecular Cloning (Cold Spring Harbor Laboratory, Cold Spring Harbor, New York; 2000).

    Google Scholar 

  16. Bahler, J. et al. Yeast 14, 943–951 (1998).

    Article  CAS  Google Scholar 

  17. Benito, J., Martin-Castellanos, C. & Moreno, S. EMBO J. 17, 482–497 (1998).

    Article  CAS  Google Scholar 

  18. Gordon, C., McGurk, G., Wallace, M. & Hastie, N. D. J. Biol. Chem. 271, 5704–5711 (1996).

    Article  CAS  Google Scholar 

  19. Dubiel, W. & Gordon, C. Curr. Biol. 9, R554–R557 (1999).

    Article  CAS  Google Scholar 

  20. Moreno, S., Klar, A. & Nurse, P. Methods Enzymol. 194, 793–823 (1990).

    Google Scholar 

  21. Beal, R. E. et al. Proc. Natl Acad. Sci. USA 93, 861–866 (1996).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank W. Dubiel and K. Ferrell for advice and help with multi-ubiquitin binding experiments; C. Landgraf and R. Volkmer-Engert for advice on the BIAcore experiments; R. Layfield for advice on using the anti-ubiquitin antibody for western blot analysis; S. Moreno for the anti-Rum1 antibody; P. McLaughlin for spotting the homology between the Mud1 protein and the aspartate protease; C. Pickart for providing lysine-48-linked multi-ubiquitin chains and for comments on the manuscript; P. Perry for advice on microscopy; S. Bruce, D. Stuart and N. Davidson for photography; and K. Hendil and N. Hastie for advice, encouragement and comments on the manuscript. This work was supported by Medical Research Council funding (to C.G.), the Danish Research Academy (to R.H.-P.) and the Deutsche Forschungsgemeinschaft (to M.S.).

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  1. Caroline R.M. Wilkinson

    Present address: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts, 02115, USA

Authors and Affiliations

  1. MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK

    Caroline R.M. Wilkinson, Michael Seeger, Rasmus Hartmann-Petersen, Miranda Stone, Mairi Wallace, Colin Semple & Colin Gordon

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  1. Caroline R.M. Wilkinson
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Correspondence to Colin Gordon.

Supplementary information

Supplementary figures

Figure S1 Proteins in fission yeast containing a UBA domain. (PDF 23 kb)

Figure S2 Surface plasmon resonance measurements of Mud1 binding to tetra-ubiquitin.

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Wilkinson, C., Seeger, M., Hartmann-Petersen, R. et al. Proteins containing the UBA domain are able to bind to multi-ubiquitin chains. Nat Cell Biol 3, 939–943 (2001). https://doi.org/10.1038/ncb1001-939

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