This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Background: O-GlcNAc (b-N-acetylglucosamine) is a protein modification consisting of an N-acetylglucosamine residue attached to serines or threonines on hundreds of cytoplasmic and nuclear proteins. The protein O-GlcNAc transferase (OGT) catalyzes the addition of the sugar moiety. During mitosis, OGT localizes to discrete structures, and elevated levels of OGT produce aneuploidy, a hallmark of cancer. Rationale: This research is driven by the hypothesis that OGT forms unique holoenzyme complexes with specific proteins during mitosis. The rationale behind this research is that once the mechanism behind mitotic targeting of OGT is understood, these interactions can be manipulated by new and highly specific pharmacological approaches resulting in treatments for cancer. Study Questions: What is unclear is how increased OGT protein expression causes aneuploidy. If OGT modifies hundreds of proteins at M phase, then how is OGT targeted to specific substrates? Is the aneuploidy phenotype due to enzymatic activity or does OGT act as a scaffold for mitotic proteins? How does Aurora Kinase B interact with OGT? Study Design: We will employ live cell imaging to study the kinetics of OGT localization through mitosis, use mass spectrometry to identify novel interacting proteins, and lastly map the interaction between OGT and its known binding partner Aurora Kinase B. Outcome Measures: Successful completion of the this aim will provide information on the structures OGT localizes too, identify novel OGT targeting proteins, and finally we will map the interacting domains between OGT and Aurora Kinase B and determine how disruption of this interaction alters M phase progression.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR024214-05
Application #
8360686
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2011-07-01
Project End
2012-08-31
Budget Start
2011-07-01
Budget End
2012-12-30
Support Year
5
Fiscal Year
2011
Total Cost
$216,633
Indirect Cost
Name
University of Kansas
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160
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