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.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
Project #
Application #
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Kansas
Anatomy/Cell Biology
Schools of Medicine
Kansas City
United States
Zip Code
Pohler, Ky G; Green, Jonathan A; Moley, Laura A et al. (2017) Circulating microRNA as candidates for early embryonic viability in cattle. Mol Reprod Dev 84:731-743
Rogers, Robert S; Tungtur, Sudheer; Tanaka, Tomohiro et al. (2017) Impaired Mitophagy Plays a Role in Denervation of Neuromuscular Junctions in ALS Mice. Front Neurosci 11:473
Navakanitworakul, Raphatphorn; Hung, Wei-Ting; Gunewardena, Sumedha et al. (2016) Characterization and Small RNA Content of Extracellular Vesicles in Follicular Fluid of Developing Bovine Antral Follicles. Sci Rep 6:25486
Aleksandrova, Anastasiia; Czirok, Andras; Kosa, Edina et al. (2015) The endoderm and myocardium join forces to drive early heart tube assembly. Dev Biol 404:40-54
Nishimune, Hiroshi; Stanford, John A; Mori, Yasuo (2014) Role of exercise in maintaining the integrity of the neuromuscular junction. Muscle Nerve 49:315-24
Wang, Huizhen; Larson, Melissa; Jablonka-Shariff, Albina et al. (2014) Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice. Proc Natl Acad Sci U S A 111:5735-40
Zhang, Yu-Kun Jennifer; Lu, Hong; Klaassen, Curtis D (2013) Expression of human CAR splicing variants in BAC-transgenic mice. Toxicol Sci 132:142-50
Elsarraj, Hanan S; Hong, Yan; Valdez, Kelli et al. (2013) A novel role of microRNA146b in promoting mammary alveolar progenitor cell maintenance. J Cell Sci 126:2446-58
Galvin-Burgess, Katherine E; Travis, Emily D; Pierson, Kelsey E et al. (2013) TGF-?-superfamily signaling regulates embryonic stem cell heterogeneity: self-renewal as a dynamic and regulated equilibrium. Stem Cells 31:48-58
Wouthuyzen-Bakker, Marjan; Bijvelds, Marcel J C; de Jonge, Hugo R et al. (2012) Effect of antibiotic treatment on fat absorption in mice with cystic fibrosis. Pediatr Res 71:4-12

Showing the most recent 10 out of 52 publications