Document Detail


Role of glutaredoxin 2 and cytosolic thioredoxins in cysteinyl-based redox modification of the 20S proteasome.
MedLine Citation:
PMID:  18435761     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The yeast 20S proteasome is subject to sulfhydryl redox alterations, such as the oxidation of cysteine residues (Cys-SH) into cysteine sulfenic acid (Cys-SOH), followed by S-glutathionylation (Cys-S-SG). Proteasome S-glutathionylation promotes partial loss of chymotrypsin-like activity and post-acidic cleavage without alteration of the trypsin-like proteasomal activity. Here we show that the 20S proteasome purified from stationary-phase cells was natively S-glutathionylated. Moreover, recombinant glutaredoxin 2 removes glutathione from natively or in vitro S-glutathionylated 20S proteasome, allowing the recovery of chymotrypsin-like activity and post-acidic cleavage. Glutaredoxin 2 deglutathionylase activity was dependent on its entry into the core particle, as demonstrated by stimulating S-glutathionylated proteasome opening. Under these conditions, deglutathionylation of the 20S proteasome and glutaredoxin 2 degradation were increased when compared to non-stimulated samples. Glutaredoxin 2 fragmentation by the 20S proteasome was evaluated by SDS-PAGE and mass spectrometry, and S-glutathionylation was evaluated by either western blot analyses with anti-glutathione IgG or by spectrophotometry with the thiol reactant 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole. It was also observed in vivo that glutaredoxin 2 was ubiquitinated in cellular extracts of yeast cells grown in glucose-containing medium. Other cytoplasmic oxido-reductases, namely thioredoxins 1 and 2, were also active in 20S proteasome deglutathionylation by a similar mechanism. These results indicate for the first time that 20S proteasome cysteinyl redox modification is a regulated mechanism coupled to enzymatic deglutathionylase activity.
Authors:
Gustavo M Silva; Luis E S Netto; Karen F Discola; Gilberto M Piassa-Filho; Daniel C Pimenta; José A Bárcena; Marilene Demasi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-04-23
Journal Detail:
Title:  The FEBS journal     Volume:  275     ISSN:  1742-464X     ISO Abbreviation:  FEBS J.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-15     Completed Date:  2008-07-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  2942-55     Citation Subset:  IM    
Affiliation:
Instituto Butantan, Laboratório de Bioquímica e Biofísica, São Paulo, Brazil, and Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, Brazil.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Cloning, Molecular
Cysteine / chemistry*
Cytosol / metabolism*
Gene Expression Regulation, Fungal*
Glutaredoxins / metabolism,  physiology*
Glutathione / chemistry,  metabolism
Hydrolysis
Models, Biological
Oxidation-Reduction
Proteasome Endopeptidase Complex / chemistry,  metabolism*
Saccharomyces cerevisiae / metabolism*
Thioredoxins / metabolism*
Chemical
Reg. No./Substance:
0/Glutaredoxins; 52-90-4/Cysteine; 52500-60-4/Thioredoxins; 70-18-8/Glutathione; EC 3.4.25.1/Proteasome Endopeptidase Complex

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


Previous Document:  Alternative binding proteins: affibody binding proteins developed from a small three-helix bundle sc...
Next Document:  Dynamin-like protein-dependent formation of Woronin bodies in Saccharomyces cerevisiae upon heterolo...