3 years ago

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

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

Summary

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.

Publisher URL: http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31268-8

DOI: 10.1016/j.celrep.2017.09.007

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