Role of CDK4/6 in regulating Rb and the restriction point
Abstract/Contents
- Abstract
- Cells escape the need for mitogens at a restriction point several hours before entering S phase. The retinoblastoma protein Rb is a key inhibitor of cell-cycle progression, and irreversible inactivation of Rb via full phosphorylation (hyperphosphorylation) is thought to underpin the restriction point. CDK4/6 has been proposed to initiate Rb phosphorylation before cyclin E/A-CDK completes hyperphosphorylation in a self-sustaining positive feedback loop, providing a plausible molecular model for the transition to mitogen independence at the restriction point. Using single-cell microscopy, we unexpectedly found that cyclin E/A-CDK activity can only maintain Rb hyperphosphorylation from the onset of S phase, while CDK4/6 activity is required to maintain Rb hyperphosphorylation throughout G1. Mitogen removal results in a gradual loss of CDK4/6 activity with a high likelihood of cells sustaining Rb hyperphosphorylation until S phase, at which point cyclin E/A-CDK activity takes over. Thus, it is short-term memory, or transient hysteresis, in CDK4/6 activity following mitogen removal that sustains Rb hyperphosphorylation, demonstrating a probabilistic, rather than irreversible, aspect to cell-cycle commitment.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Chung, Mingyu |
|---|---|
| Degree supervisor | Meyer, Tobias |
| Thesis advisor | Meyer, Tobias |
| Thesis advisor | Ferrell, James Ellsworth |
| Thesis advisor | Wang, Bo, (Researcher in bioengineering) |
| Degree committee member | Ferrell, James Ellsworth |
| Degree committee member | Wang, Bo, (Researcher in bioengineering) |
| Associated with | Stanford University, Department of Chemical and Systems Biology. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Mingyu Chung. |
|---|---|
| Note | Submitted to the Department of Chemical and Systems Biology. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Mingyu Chung
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