The nascent polypeptide-associated complex is a key regulator of proteostasis


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KIRSTEIN-MILES, Janine, Annika SCIOR, Elke DEUERLING, Richard MORIMOTO, 2013. The nascent polypeptide-associated complex is a key regulator of proteostasis. In: The EMBO Journal. 32(10), pp. 1451-1468. ISSN 0261-4189. eISSN 1460-2075. Available under: doi: 10.1038/emboj.2013.87

@article{KirsteinMiles2013-05-15nasce-24498, title={The nascent polypeptide-associated complex is a key regulator of proteostasis}, year={2013}, doi={10.1038/emboj.2013.87}, number={10}, volume={32}, issn={0261-4189}, journal={The EMBO Journal}, pages={1451--1468}, author={Kirstein-Miles, Janine and Scior, Annika and Deuerling, Elke and Morimoto, Richard} }

Scior, Annika terms-of-use The adaptation of protein synthesis to environmental and physiological challenges is essential for cell viability. Here, we show that translation is tightly linked to the protein folding environment of the cell through the functional properties of the ribosome bound chaperone NAC (nascent<br />polypeptide-associated complex). Under non-stress conditions, NAC associates with ribosomes to promote translation and protein folding. When proteostasis is imbalanced, NAC relocalizes from a ribosome-associated state to protein aggregates in its role as a chaperone. This results in a functional depletion of NAC from the ribosome that diminishes<br />translational capacity and the flux of nascent proteins. Depletion of NAC from polysomes and re-localisation to protein aggregates is observed during ageing, in response to heat shock and upon expression of the highly aggregation-prone polyglutamine-expansion proteins and Ab-peptide. These results demonstrate that NAC has a central role as a proteostasis sensor to provide the cell with a regulatory feedback mechanism in which translational activity is also controlled by the folding state of the cellular proteome and the cellular response to stress. 2013-09-30T12:17:23Z 2013-05-15 Scior, Annika The nascent polypeptide-associated complex is a key regulator of proteostasis Morimoto, Richard EMBO Journal ; 32 (2013), 10. - S. 1451-1468 Deuerling, Elke Deuerling, Elke 2013-10-31T23:25:05Z Kirstein-Miles, Janine eng Morimoto, Richard Kirstein-Miles, Janine

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