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.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/625987 |
| Date | 09 1900 |
| Creators | Kwon, Jungeun Sarah, Everetts, Nicholas J., Wang, Xia, Wang, Weikang, Della Croce, Kimiko, Xing, Jianhua, Yao, Guang |
| Contributors | Univ Arizona, Dept Mol & Cellular Biol, Univ Arizona, Arizona Canc Ctr |
| Publisher | CELL PRESS |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| Rights | © 2017 The Authors. This is an open access article under the CC BY-NC-ND license. |
| Relation | http://linkinghub.elsevier.com/retrieve/pii/S2211124717312688 |
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