RGD Reference Report - Control of ubiquitination of proteins in rat tissues by ubiquitin conjugating enzymes and isopeptidases. - Rat Genome Database

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Pathways

Control of ubiquitination of proteins in rat tissues by ubiquitin conjugating enzymes and isopeptidases.

Authors: Rajapurohitam, V  Bedard, N  Wing, SS 
Citation: Rajapurohitam V, etal., Am J Physiol Endocrinol Metab 2002 Apr;282(4):E739-45.
RGD ID: 724779
Pubmed: PMID:11882492   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpendo.00511.2001   (Journal Full-text)

The activity of the ubiquitin-dependent proteolytic system in differentiated tissues under basal conditions remains poorly explored. We measured rates of ubiquitination in rat tissue extracts. Accumulation of ubiquitinated proteins increased in the presence of ubiquitin aldehyde, indicating that deubiquitinating enzymes can regulate ubiquitination. Rates of ubiquitination varied fourfold, with the highest rate in the testis. We tested whether ubiquitin-activating enzyme (E1) or ubiquitin-conjugating enzymes (E2s) could be limiting for conjugation. Immunodepletion of the E2s UBC2 or UBC4 lowered rates of conjugation similarly. Supplementation of extracts with excess UBC2 or UBC4, but not E1, stimulated conjugation. However, UBC2-stimulated rates of ubiquitination still differed among tissues, indicating that tissue differences in E3s or substrate availability may also be rate controlling. UBC2 and UBC4 stimulated conjugation half-maximally at concentrations of 10-50 and 28-44 nM, respectively. Endogenous tissue levels of UBC2, but not UBC4, appeared saturating for conjugation, suggesting that in vivo modulation of UBC4 levels can likely control ubiquitin conjugation. Thus the pool of ubiquitin conjugates and therefore the rate of degradation of proteins by this system may be controlled by E2s, E3s, and isopeptidases. The regulation of the ubiquitin pathway appears complex, but precise.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ube2nRatprotein ubiquitination  TAS  RGD 
Uba1yRatubiquitin-dependent protein catabolic process  TAS  RGD 
Ube2nRatubiquitin-dependent protein catabolic process  TAS  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Uba1yRatubiquitin activating enzyme activity  TAS  RGD 
Ube2nRatubiquitin-protein transferase activity  IMP  RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Uba1yRatubiquitin/proteasome degradation pathway  TAS  RGD 
Ube2nRatubiquitin/proteasome degradation pathway  IMP  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Uba1y  (ubiquitin-activating enzyme, Chr Y)
Ube2n  (ubiquitin-conjugating enzyme E2N)


Additional Information