Controlling Depth of Cellular Quiescence by an Rb-E2F Network Switch

Jungeun Sarah Kwon, Nicholas J. Everetts, Xia Wang, Weikang Wang, Kimiko Della Croce, Jianhua Xing, Guang Yao

Research output: Research - peer-reviewArticle

Abstract

Quiescence is a non-proliferative cellular state that is critical to tissue repair and regeneration. Although often described as the G0 phase, quiescence is not a single homogeneous state. As cells remain quiescent for longer durations, they move progressively deeper and display a reduced sensitivity to growth signals. Deep quiescent cells, unlike senescent cells, can still re-enter the cell cycle under physiological conditions. Mechanisms controlling quiescence depth are poorly understood, representing a currently underappreciated layer of complexity in growth control. Here, we show that the activation threshold of a Retinoblastoma (Rb)-E2F network switch controls quiescence depth. Particularly, deeper quiescent cells feature a higher E2F-switching threshold and exhibit a delayed traverse through the restriction point (R-point). We further show that different components of the Rb-E2F network can be experimentally perturbed, following computer model predictions, to coarse- or fine-tune the E2F-switching threshold and drive cells into varying quiescence depths. Cellular quiescence is not a single homogeneous state but displays different depths. Kwon et al. now show that quiescence depth is controlled by the activation threshold of a bistable Rb-E2F network switch, which can be coarse- or fine-tuned by different network components to change the growth responses of quiescent cells.

LanguageEnglish (US)
Pages3223-3235
Number of pages13
JournalCell Reports
Volume20
Issue number13
DOIs
StatePublished - Sep 26 2017

Fingerprint

Switches
Retinoblastoma
Chemical activation
Growth
Network components
Repair
Cells
Tissue
Cell Cycle Resting Phase
Computer Simulation
Regeneration
Cell Cycle

Keywords

  • activation threshold
  • bistable switch
  • cell cycle entry
  • cell growth
  • cell proliferation
  • cellular quiescence
  • model simulation
  • quiescence depth
  • quiescence heterogeneity
  • Rb-E2F pathway

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Kwon, J. S., Everetts, N. J., Wang, X., Wang, W., Della Croce, K., Xing, J., & Yao, G. (2017). Controlling Depth of Cellular Quiescence by an Rb-E2F Network Switch. Cell Reports, 20(13), 3223-3235. DOI: 10.1016/j.celrep.2017.09.007

Controlling Depth of Cellular Quiescence by an Rb-E2F Network Switch. / Kwon, Jungeun Sarah; Everetts, Nicholas J.; Wang, Xia; Wang, Weikang; Della Croce, Kimiko; Xing, Jianhua; Yao, Guang.

In: Cell Reports, Vol. 20, No. 13, 26.09.2017, p. 3223-3235.

Research output: Research - peer-reviewArticle

Kwon, JS, Everetts, NJ, Wang, X, Wang, W, Della Croce, K, Xing, J & Yao, G 2017, 'Controlling Depth of Cellular Quiescence by an Rb-E2F Network Switch' Cell Reports, vol 20, no. 13, pp. 3223-3235. DOI: 10.1016/j.celrep.2017.09.007
Kwon JS, Everetts NJ, Wang X, Wang W, Della Croce K, Xing J et al. Controlling Depth of Cellular Quiescence by an Rb-E2F Network Switch. Cell Reports. 2017 Sep 26;20(13):3223-3235. Available from, DOI: 10.1016/j.celrep.2017.09.007
Kwon, Jungeun Sarah ; Everetts, Nicholas J. ; Wang, Xia ; Wang, Weikang ; Della Croce, Kimiko ; Xing, Jianhua ; Yao, Guang. / Controlling Depth of Cellular Quiescence by an Rb-E2F Network Switch. In: Cell Reports. 2017 ; Vol. 20, No. 13. pp. 3223-3235
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