Title |
Cks proteins in cell cycle control and tumorogenesis
|
Institution |
SCRIPPS RESEARCH INSTITUTE, LA JOLLA, CA
|
Principal Investigator |
REED, STEVEN
|
NCI Program Director |
N/A
|
Cancer Activity |
N/A
|
Division |
N/A
|
Funded Amount |
$44,555
|
Project Dates |
04/18/1997 - 06/30/2008
|
Fiscal Year |
2008
|
Project Type |
Grant
|
Research Topics w/ Percent Relevance |
Cancer Types w/ Percent Relevance |
Aging (5.0%)
Cancer (100.0%)
Digestive Diseases (30.0%)
|
Breast Cancer (15.0%)
Cervical Cancer (6.0%)
Colon/Rectum (15.0%)
Lung (6.0%)
Ovarian Cancer (15.0%)
Prostate (15.0%)
Stomach (15.0%)
|
Research Type |
Endogenous Factors in the Origin and Cause of Cancer
|
Abstract |
The mammalian Cks (Cks1 and Cks2) proteins are small molecular weight (
about 9kDa) proteins that are highly related evolutionarily to the yeast
S. cerevisiae CKS1 pombe suc1+ gene products (both about 13 kDa) which
interact with the cyclin dependent kinases (cdks). The yeast genes have
been shown to be essential for survival, but the exact biologic function
of either yeast protein or the mammalian proteins has not been determined.
In addition, it is known that the two human protein are encoded by
separate, and distinct, gene loci. The necessity of two separate gene
products in humans is also not clear. The Principal Investigator
originally identified the S. cerevisiae Cks gene as a high copy number
suppressor of temperature-sensitive S. pombe cdc2 and S. cerevisiae cdc28
mutations, the human isoforms, and published a number of structural and
genetic studies regarding these proteins. The studies in this proposal are
focused on determined the functional relationship between the tow mammalian
isoforms as well as examining possible role of these proteins in human
disease. To do this several strategies will be used to complement existing
data: (1) antisense experiment are proposed to assess the phenotypic
consequences of eliminating the function of Cks isoforms in cells in tissue
culture, individually and together; (2) in parallel, Cks gene knockout in
mice will be created to investigate the role (s) and essential nature of
Cks protein (s) during developing development; (3) both two-hybrid and
biochemical studies will be employed t identify downstream targets of the
Cks proteins; and (4) the human Cks genes will be mapped to chromosomal
loci as a first step in determining whether disruption of their function
genetically might be associated with human disease. |