Competition in the chaperone-client network subordinates cell-cycle entry to growth and stress

David F. Moreno; Eva Parisi; Galal Yahya; Federico Vaggi; Attila Csikász-Nagy; Martí Aldea

doi:10.26508/lsa.201800277

Competition in the chaperone-client network subordinates cell-cycle entry to growth and stress

David F. Moreno, Eva Parisi, Galal Yahya, Federico Vaggi, Attila Csikász-Nagy, Martí Aldea^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

The precise coordination of growth and proliferation has a universal prevalence in cell homeostasis. As a prominent property, cell size is modulated by the coordination between these processes in bacterial, yeast, and mammalian cells, but the underlying molecular mechanisms are largely unknown. Here, we show that multifunctional chaperone systems play a concerted and limiting role in cell-cycle entry, specifically driving nuclear accumulation of the G1 Cdk–cyclin complex. Based on these findings, we establish and test a molecular competition model that recapitulates cell-cycle-entry dependence on growth rate. As key predictions at a single-cell level, we show that availability of the Ydj1 chaperone and nuclear accumulation of the G1 cyclin Cln3 are inversely dependent on growth rate and readily respond to changes in protein synthesis and stress conditions that alter protein folding requirements. Thus, chaperone workload would subordinate Start to the biosynthetic machinery and dynamically adjust proliferation to the growth potential of the cell.

Original language	English
Article number	e201800277
Journal	Life Science Alliance
Volume	2
Issue number	2
Early online date	15 Apr 2019
DOIs	https://doi.org/10.26508/lsa.201800277
Publication status	Published - 15 Apr 2019

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10.26508/lsa.201800277

Competition in the chaperone-client_MORENO_Accepted8April2019Publishedonline15April2019_GOLD VoR (CC BY)Final published version, 2.52 MBLicence: CC BY

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abstract = "The precise coordination of growth and proliferation has a universal prevalence in cell homeostasis. As a prominent property, cell size is modulated by the coordination between these processes in bacterial, yeast, and mammalian cells, but the underlying molecular mechanisms are largely unknown. Here, we show that multifunctional chaperone systems play a concerted and limiting role in cell-cycle entry, specifically driving nuclear accumulation of the G1 Cdk–cyclin complex. Based on these findings, we establish and test a molecular competition model that recapitulates cell-cycle-entry dependence on growth rate. As key predictions at a single-cell level, we show that availability of the Ydj1 chaperone and nuclear accumulation of the G1 cyclin Cln3 are inversely dependent on growth rate and readily respond to changes in protein synthesis and stress conditions that alter protein folding requirements. Thus, chaperone workload would subordinate Start to the biosynthetic machinery and dynamically adjust proliferation to the growth potential of the cell.",

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AU - Moreno, David F.

AU - Parisi, Eva

AU - Yahya, Galal

AU - Vaggi, Federico

AU - Csikász-Nagy, Attila

AU - Aldea, Martí

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AB - The precise coordination of growth and proliferation has a universal prevalence in cell homeostasis. As a prominent property, cell size is modulated by the coordination between these processes in bacterial, yeast, and mammalian cells, but the underlying molecular mechanisms are largely unknown. Here, we show that multifunctional chaperone systems play a concerted and limiting role in cell-cycle entry, specifically driving nuclear accumulation of the G1 Cdk–cyclin complex. Based on these findings, we establish and test a molecular competition model that recapitulates cell-cycle-entry dependence on growth rate. As key predictions at a single-cell level, we show that availability of the Ydj1 chaperone and nuclear accumulation of the G1 cyclin Cln3 are inversely dependent on growth rate and readily respond to changes in protein synthesis and stress conditions that alter protein folding requirements. Thus, chaperone workload would subordinate Start to the biosynthetic machinery and dynamically adjust proliferation to the growth potential of the cell.

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Competition in the chaperone-client network subordinates cell-cycle entry to growth and stress

Abstract

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