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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Jentsch, S. & Pyrowolakis, G. Trends Cell. Biol. 10, 335–342 (2000).
Schauber, C. et al. Nature 391, 715–718 (1998).
Funakoshi, M., Sasaki, T., Nishimoto, T. & Kobayashi, H. Proc. Natl Acad. Sci. USA 99, 745–750 (2002).
Wilkinson, C. R. M. et al. Nature Cell Biol. 3, 939–943 (2001).
Kleijnen, M. F. et al. Mol. Cell 6, 409–419 (2000).
Russell, S. J., Reed, S. H., Huang, W., Friedberg, E. C. & Johnston, S. A. Mol. Cell 3, 687–695 (1999).
Lambertson, D., Chen, L. & Madura K. Genetics 153, 69–79 (1999).
Ortolan, T. G. et al. Nature Cell Biol. 2, 601–608 (2000).
Hofmann, K. & Boucher, P. Trends Biochem. Sci. 21, 172–173 (1996).
Bertolaet, B. L. et al. Nature Struct. Biol. 8, 417–422 (2001).
Glickman, M. H., Rubin, D. M., Fried, V. A. & Finley, D. Mol. Cell. Biol. 18, 3149–3162 (1998).
Verma, R. et al. Mol. Biol. Cell 11, 3425–3439 (2000).
Glickman, M. H. et al. Cell 94, 615–623 (1998).
Groll, M. et al. Nature 386, 463–471 (1997).
Lupas, A., Baumeister, W. & Hofmann, K. Trends Biochem. Sci. 22, 195–196 (1997).
Kobe, B. & Kajava, A.V. Curr. Opin. Struct. Biol. 11, 725–732 (2001).
Biggins, S., Ivanovska, I. & Rose, M. D. J. Cell Biol. 133, 1331–1346 (1996).
Rao, H. & Sastry, A. J. Biol. Chem. 277, 11691–11695 (2002).
Hiyama, H. et al. J. Biol. Chem. 274, 28019–28025 (1999).
Walters, K. J., Kleijnen, M. F., Goh, A. M., Wagner, G. & Howley, P. M. Biochemstry 41, 1767–1777 (2002).
Deveraux, Q., Ustrell, V., Pickart, C. & Rechsteiner M. J. Biol. Chem. 269, 7059–7061 (1994).
van Nocker, S. et al. Mol. Cell. Biol. 11, 6020–6028 (1996).
Fu, H. et al. J. Biol. Chem. 273, 1970–1981 (1998).
Finley, D. Nature Cell Biol. 4, E121–E123 (2002).
Lam, Y. A., Lawson, T. G., Velayutham, M., Zweier, J. L. & Pickart, C. M. Nature 416, 763–767 (2002).
Banerjee, A., Gregory, L., Xu, Y. & Chau, V. J. Biol. Chem. 268, 5668–5675 (1993).
Verma, R., McDonald, H., Yates, J. R. III & Deshaies, R. J. Mol. Cell 8, 439–448 (2001).
Beal, R. E., Toscano-Cantaffa, D., Young, P., Rechsteiner, M. & Pickart C. M. Biochemistry 37, 2925–2934 (1998).
Braun, B. C. et al. Nature Cell Biol. 1, 221–226 (1999).
Strickland, E., Hakala, K., Thomas, P. J. & DeMartino, G. N. J. Biol. Chem. 275, 5565–5572 (2000).
Hofmann, K. & Falquet, L. Trends Biochem. Sci. 26, 347–350 (2001).
Kaelin, W. G. Jr et al. Cell 70, 351–364 (1992)
Banerjee, A., Gregory, L., Xu, Y. & Chau, V. J. Biol. Chem. 268, 5668–5675 (1993)
Zachariae, W. & Nasmyth, K. Mol. Biol. Cell. 7, 791–801 (1996).
Chen, Z. & Pickart, C. M. J. Biol. Chem. 265, 21835–21842 (1990).
Leggett, D. L. et al. Mol. Cell (in the press).
Gyuris, J., Golemis., E., Chertkov, H. & Brent, R. Cell 75, 791–803 (1993).
Cagney, G., Uetz, P. & Fields, S. Physiol. Genomics 7, 27–34 (2001).
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.).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ncb845
This article is cited by
-
Ubiquilin-2 regulates pathological alpha-synuclein
Scientific Reports (2023)
-
1H, 15N, 13C resonance assignments for proteasome shuttle factor hHR23a
Biomolecular NMR Assignments (2023)
-
Lysine deserts prevent adventitious ubiquitylation of ubiquitin-proteasome components
Cellular and Molecular Life Sciences (2023)
-
Shared and divergent phase separation and aggregation properties of brain-expressed ubiquilins
Scientific Reports (2021)
-
DNA–protein crosslink proteases in genome stability
Communications Biology (2021)