Type of Thesis
Molecular, Cellular, & Developmental Biology
Dr. James Orth
Dr. Jennifer Martin
Dr. Xiang Wang
Exportin-1 (XPO-1) is responsible for the movement of cargo proteins out of the nucleus and into the cytoplasm. Selective inhibitors of nuclear export (SINE) bind XPO-1 at cysteine-528, which results in the sequestration of cargo proteins in the nucleus. SINE drugs are currently being developed and tested in the treatment of many types of cancers. One of the cargos, p53 may play an important role in the efficacy of SINE. To test the necessity of p53 in the action of SINE drugs, matched pairs of cell lines with wildtype or functionally disrupted p53 were analyzed for differences in their cell fates after treatment. The drug Nutlin targets the p53 degradation pathway and was used in comparison to SINE. SINE-induced cell death and arrest can occur independently of p53. Nutlin induced arrest in G-1 phase independent of p53, but cell death is largely dependent on p53. The two drugs in combination result in a strong death response in cells with and without p53.
Doak, Andrea E., "With or Without You: Studying the Requirement of p53 for Anti-Cancer Responses to Nuclear Export Inhibitors" (2016). Undergraduate Honors Theses. 1188.