A precise Cdk activity threshold determines passage through the restriction point
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 |
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Form | electronic; electronic resource; remote |
Extent | 1 online resource. |
Publication date | 2017 |
Issuance | monographic |
Language | English |
Creators/Contributors
Associated with | Schwarz, Clayton | |
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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 |
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Bibliographic information
Statement of responsibility | Clayton Schwarz. |
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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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