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

Janine Kirstein-Miles, Annika Scior, Elke Deuerling*, Richard I. Morimoto

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


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 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 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 Aβ-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.

Original languageEnglish (US)
Pages (from-to)1451-1468
Number of pages18
JournalEMBO Journal
Issue number10
StatePublished - May 15 2013


  • Ageing
  • Protein synthesis
  • Proteostasis
  • Ribosome

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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