Access Type

Open Access Dissertation

Date of Award

January 2012

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Biochemistry and Molecular Biology

First Advisor

David R. Evans

Abstract

Apoptosis is a normal process in the human body. However, apoptosis is desregulated in cancer cells. Most cancer cells gain resistance to apoptosis, leading to uncontrolled proliferation. In this dissertation, we identified three proteins, associated with apoptosis pathway. 1) CAD, a large multifunctional complex that is invariably elevated in tumor cells, 2) FLASH, a large protein with multiple growth related functions and 3) FAM129B. We demonstrate that CAD could interact with FLASH by using yeast two hybrid, co-immunopreciptation and fluorescence microscopy. In addition, functional analysis using siRNA technology further indicated that CAD could co-operate with FLASH and play roles in multiple cellular processes such as cell mitosis, S phase progression and apoptosis. Moreover, we identified FAM129B, a newly discovered protein that has been implicated in metastasis of melanoma cells. My study was focused on identification of this protein in apoptosis pathway. We first demonstrated that this protein is a novel cell cell junction associated protein. Knockdown of this protein could sensitize cells to apoptotic stimuli and induce rapid apoptosis. Consistent with previous studies, we also provided evidence to show that FAM129B plays important roles in breast cancer metastasis.

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