| First Author | Kalia SK | Year | 2004 |
| Journal | Neuron | Volume | 44 |
| Issue | 6 | Pages | 931-45 |
| PubMed ID | 15603737 | Mgi Jnum | J:157888 |
| Mgi Id | MGI:4437203 | Doi | 10.1016/j.neuron.2004.11.026 |
| Citation | Kalia SK, et al. (2004) BAG5 inhibits parkin and enhances dopaminergic neuron degeneration. Neuron 44(6):931-45 |
| abstractText | 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. |
