Progression through the eukaryotic cell cycle involves the coordinated activation and inactivation of cyclin dependent kinases. One such family member, Cdk1p in a complex with Cyclin B, is activated at the G2/M transition in all eukaryotes and initiates the chain of events that ultimately lead to the phenotypic changes that occur during the progression through mitosis. The inactivation of Cdk1p-cyclin B at mitotic exit must be coordinated with respect to chromosome segregation to link nuclear and cytoplasmic divisions. This inactivation not only involves irreversible destruction of Cyclin B, but also a reversal of Cdk1p dependent phosphorylation events by the conserved Cdc14 family of protein phosphatases. We have identified the Cdc14 family member, Clp1p, in the fission yeast Schizosaccharomyces pombe, and studied how the disruption of Cdk1p phosphorylation events influences the coordinated inactivation of mitotic Cdk1p activity. Clp1p specifically disrupts the Cdk1p self-sustaining amplification loop involving Cdc25p activation and Wee1p inactivation at the exit from mitosis. This disruption is temporally regulated to occur only after Cdk1p activity wanes, involving a mechanism of direct inhibition of Clp1p phosphatase activity through Cdk1p dependent phosphorylation during early mitosis. Clp1p also participates in an auto-amplification loop during mitotic exit as it auto-catalytically reverses the inhibitory phosphorylation events to increase its activity, and prevents further inhibition of its activity by attenuating Cdk1p activity. Together, these findings point to a simple regulatory circuit that couples Cdk1p activation with its inactivation mediated through regulation of Clp1p phosphatase activity.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-04152005-100234 |
| Date | 20 April 2005 |
| Creators | Wolfe, Benjamin |
| Contributors | David Greenstein, Kathleen Gould, Brian Wadzinski, Jennifer Pietenpol, Chris Hardy |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-04152005-100234/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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