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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.
Pubmed: (View Article at PubMed) PMID:15603737
DOI: Full-text: DOI:10.1016/j.neuron.2004.11.026

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.

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CRRD Object Information
CRRD ID: 8553807
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.