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Role of Rpn11 Metalloprotease in Deubiquitination and Degradation by the 26S Proteasome

Verma, Rati and Aravind, L. and Oania, Robert and McDonald, W. Hayes and Yates, John R., III and Koonin, Eugene V. and Deshaies, Raymond J. (2002) Role of Rpn11 Metalloprotease in Deubiquitination and Degradation by the 26S Proteasome. Science, 298 (5593). pp. 611-615. ISSN 0036-8075. doi:10.1126/science.1075898.

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The 26S proteasome mediates degradation of ubiquitin-conjugated proteins. Although ubiquitin is recycled from proteasome substrates, the molecular basis of deubiquitination at the proteasome and its relation to substrate degradation remain unknown. The Rpn11 subunit of the proteasome lid subcomplex contains a highly conserved Jab1/MPN domain–associated metalloisopeptidase (JAMM) motif—EX_(n)HXHX_(10)D. Mutation of the predicted active-site histidines to alanine (rpn11AXA) was lethal and stabilized ubiquitin pathway substrates in yeast. Rpn11^(AXA) mutant proteasomes assembled normally but failed to either deubiquitinate or degrade ubiquitinated Sic1 in vitro. Our findings reveal an unexpected coupling between substrate deubiquitination and degradation and suggest a unifying rationale for the presence of the lid in eukaryotic proteasomes.

Item Type:Article
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URLURL TypeDescription DOIArticle
Deshaies, Raymond J.0000-0002-3671-9354
Additional Information:© 2002 American Association for the Advancement of Science 9 July 2002; accepted 7 August 2002; published online 15 August 2002. This work was supported by Howard Hughes Medical Institute (R.V. and R.J.D.) and by a grant to University of Washington ( W.H.M. and J.R.Y., UOW/RR11823-05-01). We are indebted to C. Crews for epoxomicin, K. Takeda and T. Toda for antiserum to pad1/Rpn11, T. Rinaldi for the MPR and mpr1-1 strains, M. Hochstrasser for ubp6, C. H. Chung for Ubp6 antiserum, G. Alexandru and K. Nasmyth for the GAL-CLB2-HA3 strain, and the Deshaies lab members for critical comments.
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
University of WashingtonUOW/RR11823- 05-01
Issue or Number:5593
Record Number:CaltechAUTHORS:20141118-131459067
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Official Citation:Verma, R., Aravind, L., Oania, R., McDonald, W. H., Yates, J. R., Koonin, E. V., & Deshaies, R. J. (2002). Role of Rpn11 Metalloprotease in Deubiquitination and Degradation by the 26S Proteasome. Science, 298(5593), 611-615. doi: 10.1126/science.1075898
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:51910
Deposited By: Jason Perez
Deposited On:18 Nov 2014 22:21
Last Modified:10 Nov 2021 19:17

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