Undergraduate Honors Theses

Thesis Defended

Spring 2016

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Molecular, Cellular, & Developmental Biology

First Advisor

Dr. James Orth

Second Advisor

Dr. Jennifer Martin

Third Advisor

Dr. Xiang Wang

Abstract

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.

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