A Precise Cdk Activity Threshold Determines Passage through the Restriction Point

被引：67

作者：

Schwarz, Clayton ^{[1
]}

Johnson, Amy ^{[1
]}

Koivomagi, Mardo ^{[1
]}

Zatulovskiy, Evgeny ^{[1
]}

Kravitz, Carolyn J. ^{[1
]}

Doncic, Andreas ^{[2
,3
]}

Skotheim, Jan M. ^{[1
]}

机构：

[1] Stanford Univ, Dept Biol, Stanford, CA 94305 USA

[2] UT Southwestern Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA

[3] UT Southwestern Med Ctr, Green Ctr Syst Biol, Dallas, TX 75390 USA

来源：

MOLECULAR CELL | 2018年 / 69卷 / 02期

关键词：

PROLIFERATION-QUIESCENCE DECISION; CELL-CYCLE; NEGATIVE REGULATORS; KINASE INHIBITORS; DNA-DAMAGE; PROTEIN; G1; GROWTH; PHASE; PHOSPHORYLATION;

D O I：

10.1016/j.molcel.2017.12.017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：253 / +

页数：17

共 61 条

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