Document Detail

An ATP-stabilized inhibitor of the proteasome is a component of the 1500-kDa ubiquitin conjugate-degrading complex.
MedLine Citation:
PMID:  1317579     Owner:  NLM     Status:  MEDLINE    
Proteins conjugated to ubiquitin are degraded by a 26S (1500-kDa) proteolytic complex that, in reticulocyte extracts, can be formed by the association of three factors: CF-1, CF-2, and CF-3. One of these factors, CF-3, has been shown to be the proteasome, a 650-kDa multicatalytic protease complex. We have purified a 250-kDa inhibitor of the proteasome and shown that it corresponds to CF-2. In the presence or absence of ATP, this factor inhibited hydrolysis by the proteasome of both fluorogenic tetrapeptides and protein substrates. When the inhibitor, proteasome, and CF-1 were incubated together in the presence of ATP and Mg2+, degradation of ubiquitin-125I-lysozyme occurred. Both the inhibitory activity and the ability to reconstitute ubiquitin-125I-lysozyme degradation were very labile at 42 degrees C, but both activities were stabilized by ATP or a nonhydrolyzable ATP analog. SDS/PAGE indicated that the 250-kDa inhibitor fraction contained a major subunit of 40 kDa (plus some minor bands). The 125I-labeled inhibitor and purified proteasome formed a complex. When CF-1, ATP, and Mg2+ were also present, the 125I-labeled inhibitor along with the proteasome formed a complex of 1500 kDa. The inhibitor (CF-2) thus appears to be an ATP-binding component that regulates proteolysis within the 1500-kDa complex.
J Driscoll; J Frydman; A L Goldberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  89     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1992 Jun 
Date Detail:
Created Date:  1992-06-26     Completed Date:  1992-06-26     Revised Date:  2010-09-07    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4986-90     Citation Subset:  IM    
Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, MA 02115.
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MeSH Terms
Adenosine Triphosphate / metabolism*
Cysteine Endopeptidases / chemistry,  metabolism*
Macromolecular Substances
Molecular Weight
Multienzyme Complexes / chemistry,  metabolism*
Protease Inhibitors / chemistry*
Proteasome Endopeptidase Complex
Proteins / metabolism*
Ubiquitins / metabolism*
Reg. No./Substance:
0/Macromolecular Substances; 0/Multienzyme Complexes; 0/Protease Inhibitors; 0/Proteins; 0/Ubiquitins; 56-65-5/Adenosine Triphosphate; EC 3.4.22.-/Cysteine Endopeptidases; EC Endopeptidase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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