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J Biol Chem. 2005 Dec 2;280(48):39907-13. Epub 2005 Sep 29.

Proteasomal degradation of mutant superoxide dismutases linked to amyotrophic lateral sclerosis.

Author information

1
Laboratory of Biochemistry, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-0812, USA.

Abstract

Mutations in copper-zinc superoxide dismutase cause the neurodegenerative disease amyotrophic lateral sclerosis. Many of the mutant proteins have increased turnover in vivo and decreased thermal stability. Here we show that purified, metal-free superoxide dismutases are degraded in vitro by purified 20 S proteasome in the absence of ATP and without ubiquitinylation, whereas their metal-bound counterparts are not. The rate of degradation by the proteasome varied among the mutants studied, and the rate correlated with the in vivo half-life. The monomeric forms of both mutant and wild-type superoxide dismutase are particularly susceptible to degradation by the proteasome. Exposure of hydrophobic regions as a consequence of decreased thermal stability may allow the proteasome to recognize these molecules as non-native.

PMID:
16195234
DOI:
10.1074/jbc.M506247200
[Indexed for MEDLINE]
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