Date of Award

5-2016

Document Type

Thesis

Degree Name

Master of Science (MS)

College/School

College of Science and Mathematics

Department/Program

Biology

Thesis Sponsor/Dissertation Chair/Project Chair

Carlos Molina

Committee Member

John Gaynor

Committee Member

Sandra Adams

Abstract

Inducible cAMP Early Repressor (ICER) is a transcriptional repressor that regulates the expression of cAMP inducible genes. ICER has recently garnered attention because of cAMP’s implication in oncogenesis. ICER is shown to be downregulated in melanomas by the means of the ubiquitin-proteasome pathway. It is marked for degradation by ubiquitination on its lysine residues. By rescuing ICER levels in cancer cells, it is hypothesized that it may be possible to reverse the adverse progression of melanoma tumor growth. One possible way of rescuing ICER is by making it unavailable for ubiquitination by altering its ubiquitination sites. Special mutant ICERs that have their lysines mutated may offer the answer. Consequently, due to its nature as a transcription factor, ICER must be localized in the nucleus in order to function properly. Through immunocytochemistry, Western blotting, luciferase assay, and TUNEL apoptosis analyses of SK-MEL-24 cancer cell lysine knockout mutants, we were able to show strong nuclear subcellular localization of our mutant ICERs and efficient binding to DNA, a requirement for a transcription factor. This could potentially lead to further study of ICER as a cancer treatment.

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