Novel role for the CDK-activating kinase Cak1 in actively growing cells

Author

Su Hwa Kim, University of Tennessee, Knoxville

Date of Award

8-2008

Degree Type

Thesis

Degree Name

Master of Science

Major

Biochemistry and Cellular and Molecular Biology

Major Professor

Ana Kitazono

Committee Members

Elizabeth Howell, Gladys Alexandre

Abstract

Cdc28 is the main cyclin-dependent kinase (CDK) directing the yeast cell cycle. Besides cyclin binding, Cdc28 requires phosphorylation by Cak1 (CDK-activating kinase) to achieve full activity. In previous work, our laboratory isolated carboxy-terminal cdc28^CST mutants that display high temperature sensitivity and chromosome instability. These phenotypes are suppressed by increasing the copy numbers of Cak1 in its catalytically active or inactive form. The cdc28^CST mutants are also extremely sensitive to changes in Cak1 integrity and dosage. These results indicated that besides the activating phosphorylation by Cak1, the interaction between Cak1 and the carboxyl terminus of Cdc28 is important to maintain stable and active Cdc28 complexes. In this thesis, I discuss recent results that suggest that Cdc28 is highly dependent on Cak1 levels, even in wild type cells. Because actively growing cells require cycles of high CDK activity, we hypothesize that this can be achieved only by maintaining an optimum Cdc28:Cak1 ratio. We found that alteration of this ratio by increasing Cdc28 copy numbers is deleterious, but this effect is suppressed by concomitant increase of the copy numbers of Cak1 (catalytically active or inactive). We found that there is a very good correlation between active cell growth and Cak1 levels. Based on these results we propose the following model: When cells sense depletion of nutrients and must cease dividing, Cak1 is degraded to alter the Cdc28:Cak1 ratio leading to quick inactivation of Cdc28. According to this model, Cak1 functions as an assembly factor for Cdc28 CDK complexes coordinating nutrient availability and cell growth in yeast.

Recommended Citation

Kim, Su Hwa, "Novel role for the CDK-activating kinase Cak1 in actively growing cells. " Master's Thesis, University of Tennessee, 2008.
https://trace.tennessee.edu/utk_gradthes/3665