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Protein homeostasis: live long, won't prosper

Abstract

Protein turnover is an effective way of maintaining a functional proteome, as old and potentially damaged polypeptides are destroyed and replaced by newly synthesized copies. An increasing number of intracellular proteins, however, have been identified that evade this turnover process and instead are maintained over a cell's lifetime. This diverse group of long-lived proteins might be particularly prone to accumulation of damage and thus have a crucial role in the functional deterioration of key regulatory processes during ageing.

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Figure 1: Long-lived proteins and the accumulation of damage.
Figure 2: Crystallin is a long-lived lens protein important for eye function.
Figure 3: Specific components of the NPC are long-lived.

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Acknowledgements

The authors thank members of the Hetzer laboratory and E.Q. Toyama for helpful suggestions and critical reading of the manuscript. B.H.T is supported by the Hewitt Foundation; M.W.H by the Ellison Medical Foundation, by the US National Institutes of Health (NIH) (R01GM098749) and the National Cancer Institute (award number P30CA014195).

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Toyama, B., Hetzer, M. Protein homeostasis: live long, won't prosper. Nat Rev Mol Cell Biol 14, 55–61 (2013). https://doi.org/10.1038/nrm3496

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