Controlling Depth of Cellular Quiescence by an Rb-E2F Network Switch
AuthorKwon, Jungeun Sarah
Everetts, Nicholas J.
Della Croce, Kimiko
AffiliationUniv Arizona, Dept Mol & Cellular Biol
Univ Arizona, Arizona Canc Ctr
cell cycle entry
MetadataShow full item record
CitationControlling Depth of Cellular Quiescence by an Rb-E2F Network Switch 2017, 20 (13):3223 Cell Reports
Rights© 2017 The Authors. This is an open access article under the CC BY-NC-ND license.
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AbstractQuiescence 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.
VersionFinal published version
SponsorsNSF [DMS-1463137, DMS-1418172]; NIH [GM084905]; DARPA [WF911NF-14-1-0395]; NSF of China ; Anhui Province [1508085SQC202]
Except where otherwise noted, this item's license is described as © 2017 The Authors. This is an open access article under the CC BY-NC-ND license.