A precise Cdk activity threshold determines passage through the restriction point

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Abstract/Contents

Abstract
At the restriction point (R), mammalian cells irreversibly commit to divide. R has been viewed as a point in G1 after growth factor signaling initiates a positive feedback loop of Cdk activity. However, recent studies 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 classified by a few critical protein activities.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2017
Issuance monographic
Language English

Creators/Contributors

Associated with Schwarz, Clayton
Associated with Stanford University, Department of Biology.
Primary advisor Skotheim, Jan, 1977-
Thesis advisor Skotheim, Jan, 1977-
Thesis advisor Block, Steven M
Thesis advisor Lipsick, Joseph Steven, 1955-
Thesis advisor Nelson, William
Advisor Block, Steven M
Advisor Lipsick, Joseph Steven, 1955-
Advisor Nelson, William

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Clayton Schwarz.
Note Submitted to the Department of Biology.
Thesis Thesis (Ph.D.)--Stanford University, 2017.
Location electronic resource

Access conditions

Copyright
© 2017 by Clayton Joseph Schwarz
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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