RRC ID 81233
Author Schwarz C, Johnson A, Kõivomägi M, Zatulovskiy E, Kravitz CJ, Doncic A, Skotheim JM.
Title A Precise Cdk Activity Threshold Determines Passage through the Restriction Point.
Journal Mol Cell
Abstract At the restriction point (R), mammalian cells irreversibly commit to divide. R has been viewed as a point in G1 that is passed when growth factor signaling initiates a positive feedback loop of Cdk activity. However, recent studies have cast doubt on this model by claiming R occurs prior to positive feedback activation in G1 or even before completion of the previous cell cycle. Here we reconcile these results and show that whereas many commonly used cell lines do not exhibit a G1 R, primary fibroblasts have a G1 R that is defined by a precise Cdk activity threshold and the activation of cell-cycle-dependent transcription. A simple threshold model, based solely on Cdk activity, predicted with more than 95% accuracy whether individual cells had passed R. That a single measurement accurately predicted cell fate shows that the state of complex regulatory networks can be assessed using a few critical protein activities.
Volume 69(2)
Pages 253-264.e5
Published 2018-1-18
DOI 10.1016/j.molcel.2017.12.017
PII S1097-2765(17)30969-3
PMID 29351845
PMC PMC5790185
MeSH Animals Cell Cycle / physiology Cell Cycle Checkpoints / physiology* Cell Cycle Proteins / metabolism Cell Division Cell Line Cyclin-Dependent Kinase 2 / metabolism* Cyclin-Dependent Kinase 2 / physiology Cyclin-Dependent Kinases / metabolism Fibroblasts / physiology G1 Phase / physiology G1 Phase Cell Cycle Checkpoints / physiology* Humans Phosphorylation Primary Cell Culture Signal Transduction
Resource
DNA material CSII-EF-MCS (RDB04378)