Oxidation of the cysteine-rich regions of parkin perturbs its E3 ligase activity and contributes to protein aggregation.

ABSTRACT:

Background

Accumulation of aberrant proteins to form Lewy bodies (LBs) is a hallmark of Parkinson's disease (PD). Ubiquitination-mediated degradation of aberrant, misfolded proteins is critical for maintaining normal cell function. Emerging evidence suggests that oxidative/nitrosative stress compromises the precisely-regulated network of ubiquitination in PD, particularly affecting parkin E3 ligase activity, and contributes to the accumulation of toxic proteins and neuronal cell death.

Results

To gain insight into the mechanism whereby cell stress alters parkin-mediated ubiquitination and LB formation, we investigated the effect of oxidative stress. We found significant increases in oxidation (sulfonation) and subsequent aggregation of parkin in SH-SY5Y cells exposed to the

SUBMITTER: Meng F 

PROVIDER: S-EPMC3120712 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature