Document Detail

Lysine 63-linked polyubiquitin chain may serve as a targeting signal for the 26S proteasome.
MedLine Citation:
PMID:  19153599     Owner:  NLM     Status:  MEDLINE    
Recruitment of substrates to the 26S proteasome usually requires covalent attachment of the Lys48-linked polyubiquitin chain. In contrast, modifications with the Lys63-linked polyubiquitin chain and/or monomeric ubiquitin are generally thought to function in proteasome-independent cellular processes. Nevertheless, the ubiquitin chain-type specificity for the proteasomal targeting is still poorly understood, especially in vivo. Using mass spectrometry, we found that Rsp5, a ubiquitin-ligase in budding yeast, catalyzes the formation of Lys63-linked ubiquitin chains in vitro. Interestingly, the 26S proteasome degraded well the Lys63-linked ubiquitinated substrate in vitro. To examine whether Lys63-linked ubiquitination serves in degradation in vivo, we investigated the ubiquitination of Mga2-p120, a substrate of Rsp5. The polyubiquitinated p120 contained relatively high levels of Lys63-linkages, and the Lys63-linked chains were sufficient for the proteasome-binding and subsequent p120-processing. In addition, Lys63-linked chains as well as Lys48-linked chains were detected in the 26S proteasome-bound polyubiquitinated proteins. These results raise the possibility that Lys63-linked ubiquitin chain also serves as a targeting signal for the 26S proteaseome in vivo.
Yasushi Saeki; Tai Kudo; Takayuki Sone; Yoshiko Kikuchi; Hideyoshi Yokosawa; Akio Toh-e; Keiji Tanaka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-15
Journal Detail:
Title:  The EMBO journal     Volume:  28     ISSN:  1460-2075     ISO Abbreviation:  EMBO J.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-19     Completed Date:  2009-03-26     Revised Date:  2010-09-22    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  359-71     Citation Subset:  IM    
Laboratory of Frontier Science, Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo, Japan.
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MeSH Terms
Cyclin-Dependent Kinase Inhibitor Proteins
Endosomal Sorting Complexes Required for Transport
Lysine / chemistry*
Mass Spectrometry / methods
Membrane Proteins
Models, Biological
Plasmids / metabolism
Polyubiquitin / chemistry*
Proteasome Endopeptidase Complex / metabolism*
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / metabolism*
Signal Transduction
Trans-Activators / metabolism
Transcription Factors
Ubiquitin / chemistry
Ubiquitin-Protein Ligase Complexes / metabolism*
p120 GTPase Activating Protein / metabolism
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor Proteins; 0/Endosomal Sorting Complexes Required for Transport; 0/MGA2 protein, S cerevisiae; 0/Membrane Proteins; 0/SIC1 protein, S cerevisiae; 0/SPT23 protein, S cerevisiae; 0/Saccharomyces cerevisiae Proteins; 0/Trans-Activators; 0/Transcription Factors; 0/Ubiquitin; 0/p120 GTPase Activating Protein; 120904-94-1/Polyubiquitin; 56-87-1/Lysine; EC Endopeptidase Complex; EC 3.4.99.-/ATP dependent 26S protease; EC protein, S cerevisiae; EC Ligase Complexes

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