RGD Reference Report - BAG5 inhibits parkin and enhances dopaminergic neuron degeneration. - Rat Genome Database

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BAG5 inhibits parkin and enhances dopaminergic neuron degeneration.

Authors: Kalia, SK  Lee, S  Smith, PD  Liu, L  Crocker, SJ  Thorarinsdottir, TE  Glover, JR  Fon, EA  Park, DS  Lozano, AM 
Citation: Kalia SK, etal., Neuron. 2004 Dec 16;44(6):931-45.
RGD ID: 8553807
Pubmed: PMID:15603737   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuron.2004.11.026   (Journal Full-text)

Loss-of-function mutations in the parkin gene, which encodes an E3 ubiquitin ligase, are the major cause of early-onset Parkinson's disease (PD). Decreases in parkin activity may also contribute to neurodegeneration in sporadic forms of PD. Here, we show that bcl-2-associated athanogene 5 (BAG5), a BAG family member, directly interacts with parkin and the chaperone Hsp70. Within this complex, BAG5 inhibits both parkin E3 ubiquitin ligase activity and Hsp70-mediated refolding of misfolded proteins. BAG5 enhances parkin sequestration within protein aggregates and mitigates parkin-dependent preservation of proteasome function. Finally, BAG5 enhances dopamine neuron death in an in vivo model of PD, whereas a mutant that inhibits BAG5 activity attenuates dopaminergic neurodegeneration. This contrasts with the antideath functions ascribed to BAG family members and suggests a potential role for BAG5 in promoting neurodegeneration in sporadic PD through its functional interactions with parkin and Hsp70.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of protein refolding involved_inIMP 8553807PMID:15603737BHF-UCL 
negative regulation of protein ubiquitination involved_inIDA 8553807PMID:15603737BHF-UCL 
regulation of inclusion body assembly involved_inIDA 8553807PMID:15603737BHF-UCL 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
inclusion body located_inISSUniProtKB:Q9UL158553807PMID:15603737BHF-UCL 
perinuclear region of cytoplasm located_inISSUniProtKB:Q9UL158553807PMID:15603737BHF-UCL 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein-folding chaperone binding enablesIDA 8553807PMID:15603737BHF-UCL 
ubiquitin protein ligase binding enablesIPIUniProtKB:O602608553807PMID:15603737BHF-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Bag5  (BAG cochaperone 5)


Additional Information