The diverse events of the eukaryotic cell cycle are induced and coordinated by the activity of cyclin-dependent kinases, which are activated at specific times during the cell cycle when they associate with members of the cyclin family of proteins. Although much has been learned about the regulation of cyclin-dependent kinase complexes, we still know virtually nothing about the pathways used by these kinases to induce cell cycle events. In simple organisms like budding yeast, a single cyclin-dependent kinase controls all of the events of the cell cycle. It is unknown how cyclin-dependent kinases attain such specificity. One possibility is that the different cyclins serve to determine the functions of specific cyclindependent kinase complexes. The long term goal of this project will be to gain a greater understanding of the pathways used by cyclin-dependent kinases to induce the events of the cell cycle. We will focus on the pathway used by cyclin-dependent kinases in budding yeast to control bud growth during mitosis, since this pathway is particularly amenable to detailed characterization, and preliminary work has already identified one of its components. A combination of genetics and biochemistry will be used to identify additional proteins that function to control bud growth during mitosis, and these will be studied as part of a detailed characterization of the pathway. The control of bud growth is likely to utilize fundamental mechanisms, since several of the proteins known to be involved are highly conserved between humans and yeast. An understanding of the pathways used to execute mitotic events is of considerable clinical relevance, since such pathways are likely to represent good targets for drugs designed to block the division of cancer cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM053959-02
Application #
2444890
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1996-07-01
Project End
2001-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California Santa Cruz
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Santa Cruz
State
CA
Country
United States
Zip Code
95064
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Lucena, Rafael; Alcaide-Gavilán, Maria; Schubert, Katherine et al. (2018) Cell Size and Growth Rate Are Modulated by TORC2-Dependent Signals. Curr Biol 28:196-210.e4
Vadia, Stephen; Tse, Jessica L; Lucena, Rafael et al. (2017) Fatty Acid Availability Sets Cell Envelope Capacity and Dictates Microbial Cell Size. Curr Biol 27:1757-1767.e5
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McCusker, Derek; Royou, Anne; Velours, Christophe et al. (2012) Cdk1-dependent control of membrane-trafficking dynamics. Mol Biol Cell 23:3336-47
McCusker, Derek; Kellogg, Douglas R (2012) Plasma membrane growth during the cell cycle: unsolved mysteries and recent progress. Curr Opin Cell Biol 24:845-51
Egelhofer, Thea A; Villen, Judit; McCusker, Derek et al. (2008) The septins function in G1 pathways that influence the pattern of cell growth in budding yeast. PLoS One 3:e2022
McCusker, Derek; Denison, Carilee; Anderson, Scott et al. (2007) Cdk1 coordinates cell-surface growth with the cell cycle. Nat Cell Biol 9:506-15

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