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FEBS Lett. 2001 Nov 30;509(1):22-6.

alpha-synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome.

Author information

1
Cambridge Centre for Brain Repair and Neurology Department, University of Cambridge, Forvie Site, Robinson Way, CB2 2PY, Cambridge, UK.

Abstract

alpha-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 alpha-synuclein is sufficient to induce inclusion formation in SH-SY5Y cells. In this cellular model, proteasome inhibition leads to an increase of alpha-synuclein accumulation in vivo without ubiquitylation. In accordance, we find that in vitro, unmodified alpha-synuclein can be directly degraded by the 20S proteasome. These findings suggest an ubiquitin-independent mechanism of proteasomal degradation for alpha-synuclein and other natively unfolded proteins.

PMID:
11734199
DOI:
10.1016/s0014-5793(01)03115-5
[Indexed for MEDLINE]
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