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Proteasomal adaptation to environmental stress links resistance to proteotoxicity with longevity in Caenorhabditis elegans
- Yun, Chi, Stanhill, Ariel, Yang, Yun, Zhang, Yuhong, Haynes, Cole M., Xu, Chong-Feng, Neubert, Thomas A., Mor, Adam, Philips, Mark R., Ron, David
- Proceedings of the National Academy of Sciences of the United States of America 2008 v.105 no.19 pp. 7094-7099
- Caenorhabditis elegans, active sites, arsenites, gene expression, genes, genetic rescue, hypersensitivity, longevity, mammals, proteasome endopeptidase complex, protein folding, proteins, stress tolerance
- The burden of protein misfolding is believed to contribute to aging. However, the links between adaptations to conditions associated with protein misfolding and resistance to the time-dependent attrition of cellular function remain poorly understood. We report that worms lacking aip-1, a homologue of mammalian AIRAP (arsenic-inducible proteasomal 19S regulatory particle-associated protein), are not only impaired in their ability to resist exposure to arsenite but also exhibit shortened lifespan and hypersensitivity to misfolding-prone proteins under normal laboratory conditions. Mammals have a second, constitutively expressed AIRAP-like gene (AIRAPL) that also encodes a proteasome-interacting protein, which shares with AIRAP the property of enhancing peptide accessibility to the proteasome's active site. Genetic rescue experiments suggest that features common to the constitutively expressed worm AIP-1 and mammalian AIRAPL (but missing in the smaller, arsenite-inducible AIRAP) are important to lifespan extension. In worms, a single AIRAP-related protein links proteasomal adaptation to environmental stress with resistance to both proteotoxic insults and maintenance of animal life span under normal conditions.