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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.

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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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