Date of Award
Chemistry and Biochemistry
One of the hallmarks of cancer is its ability to adapt its metabolism to survive and thrive despite needing to overcome significant energy barriers and low oxygen settings in order to do so. The hypoxia-inducible factor proteins (HIFs) play important roles in the processes in which cancer fulfills these requirements. The O-linked -N-acetylglucoseamine (O-GlcNAc) can be attached to cellular proteins through O-glycosylation, and is thus considered a potential target for anticancer mechanisms. HIFs are composed of (HIF-1 and HIF-2, respectively) and subunits. This research found that O-GlcNAc is able to attach to and modify the HIF proteins. This was accomplished through the use of immunoprecipitation followed by western blot, examining nuclear extract samples prepared from human breast cancer T47D cells. The O-GlcNAc was found to attach to both HIF-1 and HIF-2, and was most prominently expressed in the presence of O-(2-Acetamido-2-deoxy-D-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc), which enhances O-GlcNAcylation by inhibiting the enzyme OGA.
Williamson, Sean, "Post-Translational Modification of Hypoxia-Inducible Factor Proteins by O-Linked -N-Acetylglucosamine in Breast Cancer Cells" (2018). Honors Theses. 846.