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Nature. 2003 Dec 18;426(6968):895-9.

Protein degradation and protection against misfolded or damaged proteins.

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  • 1Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA. alfred_goldberg@hms.harvard.edu


The ultimate mechanism that cells use to ensure the quality of intracellular proteins is the selective destruction of misfolded or damaged polypeptides. In eukaryotic cells, the large ATP-dependent proteolytic machine, the 26S proteasome, prevents the accumulation of non-functional, potentially toxic proteins. This process is of particular importance in protecting cells against harsh conditions (for example, heat shock or oxidative stress) and in a variety of diseases (for example, cystic fibrosis and the major neurodegenerative diseases). A full understanding of the pathogenesis of the protein-folding diseases will require greater knowledge of how misfolded proteins are recognized and selectively degraded.

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