Proteasomal degradation of mutant superoxide dismutases linked to amyotrophic lateral sclerosis

Luca Di Noto, Lisa J. Whitson, Xiaohang Cao, P. John Hart, Rodney L. Levine

Research output: Contribution to journalArticle

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)39907-39913
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number48
DOIs
StatePublished - Dec 2 2005

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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