Multisite phosphorylation generates ultrasensitivity in the regulation of Cdc25C by Cdk1
Abstract/Contents
- Abstract
- Multisite Phosphorylation generates ultrasensitivity in the regulation of Cdc25C by Cdk1 abstract. The mitotic phosphatase Cdc25C opposes the inhibitory activity of the mitotic kinases Wee1 and Myt1 as part of a double feedback loop system that gates entry into mitosis. The substrate for both Cdc25C and Wee1 is the kinase Cdk1, which activates Cdc25C and inhibits Wee1 via hyperphosphorylation of both proteins' N-terminal regulatory regions. This work characterizes the structure, or lack thereof, of the N-terminal regulatory domain of Cdc25C through biochemical assays and NMR analysis. Furthermore, while previous evidence has shown that the response of Wee1 phosphorylation is ultrasensitive with respect to Cdk1 activity, this work demonstrates that Cdc25C is similarly hyperphosphorylated in an ultrasensitive fashion in Xenopus extract. The ultrasensitive hyperphosphorylation of Cdc25C does not depend on competition from other Cdk1 substrates and is unchanged in a diluted extract system. The response function of Cdc25C in a simplified in vitro system remains ultrasensitive, although to a lesser extent. This mild ultrasensitive response becomes Michaelian as phosphosites are mutated, indicating that some fraction of Cdc25C's ultrasensitivity is the result of multisite phosphorylation by Cdk1. However, a significant remaining fraction of the response cannot be explained by intrinsic ultrasensitivity, and appears to be due to extract-specific factors.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Copyright date | 2010 |
| Publication date | 2009, c2010; 2009 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Trunnell, Nicole Breaux |
|---|---|
| Associated with | Stanford University, Cancer Biology Program |
| Primary advisor | Ferrell, James Ellsworth |
| Thesis advisor | Ferrell, James Ellsworth |
| Thesis advisor | Bogyo, Matthew, 1971- |
| Thesis advisor | Cimprich, Karlene |
| Thesis advisor | Stearns, Tim |
| Advisor | Bogyo, Matthew, 1971- |
| Advisor | Cimprich, Karlene |
| Advisor | Stearns, Tim |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Nicole Breaux Trunnell. |
|---|---|
| Note | Submitted to the Program in Cancer Biology. |
| Thesis | Ph.D. Stanford University 2010 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Nicole Breaux Trunnell
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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