α‐Synuclein metabolism and aggregation is linked to ubiquitin‐independent degradation by the proteasome
Top Cited Papers
- 9 November 2001
- journal article
- Published by Wiley in FEBS Letters
- Vol. 509 (1) , 22-26
- https://doi.org/10.1016/s0014-5793(01)03115-5
Abstract
α‐Synuclein has been implicated in the pathogenesis of Parkinson's disease based on mutations in familial cases of the disease and its presence in Lewy bodies. Here we show that over‐expression of wild‐type human α‐synuclein is sufficient to induce inclusion formation in SH‐SY5Y cells. In this cellular model, proteasome inhibition leads to an increase of α‐synuclein accumulation in vivo without ubiquitylation. In accordance, we find that in vitro, unmodified α‐synuclein can be directly degraded by the 20S proteasome. These findings suggest an ubiquitin‐independent mechanism of proteasomal degradation for α‐synuclein and other natively unfolded proteins.Keywords
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