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Proc Natl Acad Sci U S A. 2017 Nov 28;114(48):E10329-E10338. doi: 10.1073/pnas.1710238114. Epub 2017 Nov 13.

Proteome-wide modulation of degradation dynamics in response to growth arrest.

Author information

Department of Biology, University of Rochester, Rochester, NY 14627.
Mass Spectrometry Resource Laboratory, University of Rochester, Rochester, NY 14627.
Department of Biology, University of Rochester, Rochester, NY 14627;


In dividing cells, cytoplasmic dilution is the dominant route of clearance for long-lived proteins whose inherent degradation is slower than the cellular growth rate. Thus, as cells transition from a dividing to a nondividing state, there is a propensity for long-lived proteins to become stabilized relative to short-lived proteins, leading to alterations in the abundance distribution of the proteome. However, it is not known if cells mount a compensatory response to counter this potentially deleterious proteostatic disruption. We used a proteomic approach to demonstrate that fibroblasts selectively increase degradation rates of long-lived proteins as they transition from a proliferating to a quiescent state. The selective degradation of long-lived proteins occurs by the concurrent activation of lysosomal biogenesis and up-regulation of macroautophagy. Through this mechanism, quiescent cells avoid the accumulation of aged long-lived proteins that would otherwise result from the absence of cytoplasmic dilution by cell division.


lysosome; protein degradation; protein homeostasis; quantitative proteomics; quiescence

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Conflict of interest statement

The authors declare no conflict of interest.

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