Impairment of the ubiquitin-proteasome system by protein aggregation
- PMID: 11375494
- DOI: 10.1126/science.292.5521.1552
Impairment of the ubiquitin-proteasome system by protein aggregation
Abstract
Intracellular deposition of aggregated and ubiquitylated proteins is a prominent cytopathological feature of most neurodegenerative disorders. Whether protein aggregates themselves are pathogenic or are the consequence of an underlying molecular lesion is unclear. Here, we report that protein aggregation directly impaired the function of the ubiquitin-proteasome system. Transient expression of two unrelated aggregation-prone proteins, a huntingtin fragment containing a pathogenic polyglutamine repeat and a folding mutant of cystic fibrosis transmembrane conductance regulator, caused nearly complete inhibition of the ubiquitin-proteasome system. Because of the central role of ubiquitin-dependent proteolysis in regulating fundamental cellular events such as cell division and apoptosis, our data suggest a potential mechanism linking protein aggregation to cellular disregulation and cell death.
Comment in
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Cell biology. Protein clumps hijack cell's clearance system.Science. 2001 May 25;292(5521):1467-8. doi: 10.1126/science.292.5521.1467a. Science. 2001. PMID: 11379612 No abstract available.
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