Dataset Information

Schwarz2018-Cdk Activity Threshold Determines Passage through the Restriction Point

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.

SUBMITTER: Ahmad Zyoud

PROVIDER: BIOMD0000000918 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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			Action	DRS
	BIOMD0000000918?filename=Schwarz2018-biopax2.owl	Owl
	BIOMD0000000918?filename=Schwarz2018-biopax3.owl	Owl
	BIOMD0000000918?filename=Schwarz2018-matlab.m	Other
	BIOMD0000000918?filename=Schwarz2018.cps	Other
	BIOMD0000000918?filename=Schwarz2018.ode	Other

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A Precise Cdk Activity Threshold Determines Passage through the Restriction Point.

Schwarz Clayton C Johnson Amy A Kõivomägi Mardo M Zatulovskiy Evgeny E Kravitz Carolyn J CJ Doncic Andreas A Skotheim Jan M JM

Molecular cell 20180101 2

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 fibr ...[more]

PMID: 29351845

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