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Proteasome subunit Rpn1 binds ubiquitin-like protein domains

Abstract

The yeast protein Rad23 belongs to a diverse family of proteins that contain an amino-terminal ubiquitin-like (UBL) domain. This domain mediates the binding of Rad23 to proteasomes, which in turn promotes DNA repair and modulates protein degradation, possibly by delivering ubiquitinylated cargo to proteasomes. Here we show that Rad23 binds proteasomes by directly interacting with the base subcomplex of the regulatory particle of the proteasome. A component of the base, Rpn1, specifically recognizes the UBL domain of Rad23 through its leucine-rich-repeat-like (LRR-like) domain. A second UBL protein, Dsk2, competes with Rad23 for proteasome binding, which suggests that the LRR-like domain of Rpn1 may participate in the recognition of several ligands of the proteasome. We propose that the LRR domain of Rpn1 may be positioned in the base to allow the cargo proteins carried by Rad23 to be presented to the proteasomal ATPases for unfolding. We also report that, contrary to expectation, the base subunit Rpn10 does not mediate the binding of UBL proteins to the proteasome in yeast, although it can apparently contribute to the binding of ubiquitin chains by intact proteasomes.

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Figure 1: Rad23 associates with the base of the proteasome.
Figure 2: Rad23 binds proteasome subunit Rpn1 through its LRR-like domain.
Figure 3: Dsk2 competes with Rad23 in proteasome binding.
Figure 4: Recognition of ubiquitin-like proteins and ubiquitin conjugates (Ubn) by rpn10Δ proteasomes.

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References

  1. Jentsch, S. & Pyrowolakis, G. Trends Cell. Biol. 10, 335–342 (2000).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Funakoshi, M., Sasaki, T., Nishimoto, T. & Kobayashi, H. Proc. Natl Acad. Sci. USA 99, 745–750 (2002).

    Article  CAS  Google Scholar 

  4. Wilkinson, C. R. M. et al. Nature Cell Biol. 3, 939–943 (2001).

    Article  CAS  Google Scholar 

  5. Kleijnen, M. F. et al. Mol. Cell 6, 409–419 (2000).

    Article  CAS  Google Scholar 

  6. Russell, S. J., Reed, S. H., Huang, W., Friedberg, E. C. & Johnston, S. A. Mol. Cell 3, 687–695 (1999).

    Article  CAS  Google Scholar 

  7. Lambertson, D., Chen, L. & Madura K. Genetics 153, 69–79 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Ortolan, T. G. et al. Nature Cell Biol. 2, 601–608 (2000).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  11. Glickman, M. H., Rubin, D. M., Fried, V. A. & Finley, D. Mol. Cell. Biol. 18, 3149–3162 (1998).

    Article  CAS  Google Scholar 

  12. Verma, R. et al. Mol. Biol. Cell 11, 3425–3439 (2000).

    Article  CAS  Google Scholar 

  13. Glickman, M. H. et al. Cell 94, 615–623 (1998).

    Article  CAS  Google Scholar 

  14. Groll, M. et al. Nature 386, 463–471 (1997).

    Article  CAS  Google Scholar 

  15. Lupas, A., Baumeister, W. & Hofmann, K. Trends Biochem. Sci. 22, 195–196 (1997).

    Article  CAS  Google Scholar 

  16. Kobe, B. & Kajava, A.V. Curr. Opin. Struct. Biol. 11, 725–732 (2001).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  18. Rao, H. & Sastry, A. J. Biol. Chem. 277, 11691–11695 (2002).

    Article  CAS  Google Scholar 

  19. Hiyama, H. et al. J. Biol. Chem. 274, 28019–28025 (1999).

    Article  CAS  Google Scholar 

  20. Walters, K. J., Kleijnen, M. F., Goh, A. M., Wagner, G. & Howley, P. M. Biochemstry 41, 1767–1777 (2002).

    Article  CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  22. van Nocker, S. et al. Mol. Cell. Biol. 11, 6020–6028 (1996).

    Article  Google Scholar 

  23. Fu, H. et al. J. Biol. Chem. 273, 1970–1981 (1998).

    Article  CAS  Google Scholar 

  24. Finley, D. Nature Cell Biol. 4, E121–E123 (2002).

    Article  CAS  Google Scholar 

  25. Lam, Y. A., Lawson, T. G., Velayutham, M., Zweier, J. L. & Pickart, C. M. Nature 416, 763–767 (2002).

    Article  CAS  Google Scholar 

  26. Banerjee, A., Gregory, L., Xu, Y. & Chau, V. J. Biol. Chem. 268, 5668–5675 (1993).

    CAS  Google Scholar 

  27. Verma, R., McDonald, H., Yates, J. R. III & Deshaies, R. J. Mol. Cell 8, 439–448 (2001).

    Article  CAS  Google Scholar 

  28. Beal, R. E., Toscano-Cantaffa, D., Young, P., Rechsteiner, M. & Pickart C. M. Biochemistry 37, 2925–2934 (1998).

    Article  CAS  Google Scholar 

  29. Braun, B. C. et al. Nature Cell Biol. 1, 221–226 (1999).

    Article  CAS  Google Scholar 

  30. Strickland, E., Hakala, K., Thomas, P. J. & DeMartino, G. N. J. Biol. Chem. 275, 5565–5572 (2000).

    Article  CAS  Google Scholar 

  31. Hofmann, K. & Falquet, L. Trends Biochem. Sci. 26, 347–350 (2001).

    Article  CAS  Google Scholar 

  32. Kaelin, W. G. Jr et al. Cell 70, 351–364 (1992)

    Article  CAS  Google Scholar 

  33. Banerjee, A., Gregory, L., Xu, Y. & Chau, V. J. Biol. Chem. 268, 5668–5675 (1993)

    CAS  Google Scholar 

  34. Zachariae, W. & Nasmyth, K. Mol. Biol. Cell. 7, 791–801 (1996).

    Article  CAS  Google Scholar 

  35. Chen, Z. & Pickart, C. M. J. Biol. Chem. 265, 21835–21842 (1990).

    CAS  PubMed  Google Scholar 

  36. Leggett, D. L. et al. Mol. Cell (in the press).

  37. Gyuris, J., Golemis., E., Chertkov, H. & Brent, R. Cell 75, 791–803 (1993).

    Article  CAS  Google Scholar 

  38. Cagney, G., Uetz, P. & Fields, S. Physiol. Genomics 7, 27–34 (2001).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank C. Pickart for unanchored ubiquitin chains; K. Madura for plasmids, antibodies, and discussions; A. Toh-e for generous gifts of antibodies to proteasome subunits; M. Rose for the Dsk2 expression plasmids; S. Sadis for Uba1 and Cdc34; M. Glickman for conventionally purified proteasome; and D. Moazed and members of the Finley lab for comments on the manuscript. This work was supported by a grant from the NIH (D.F.), a grant from the Giovanni Armenise-Harvard Foundation (D.F.), National Research Service Award postdoctoral fellowships (S.E., C.N.L., and D.S.L.) and a Deutsche Forschungsgemeinschaft postdoctoral fellowship (G.D.).

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Correspondence to Daniel Finley.

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Elsasser, S., Gali, R., Schwickart, M. et al. Proteasome subunit Rpn1 binds ubiquitin-like protein domains. Nat Cell Biol 4, 725–730 (2002). https://doi.org/10.1038/ncb845

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