Date of Award

Fall 12-2021

Level of Access Assigned by Author

Open-Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biochemistry and Molecular Biology

Advisor

Joshua Kelley

Second Committee Member

Julie Gosse

Third Committee Member

Robert Gunderson

Additional Committee Members

Melissa Maginnis

Ek Han Tan

Abstract

Cell growth is reliant on the flawless orchestration of cellular signaling and is crucial to evade cancer metastasis. It is important to understand key elements of cellular processes like gene regulation and stress signaling and how they contribute to oncogenesis. Cancer cells prove exceptionally adaptive as they effectively evade cellular stress, thus encouraging a tumor hospitable environment and subsequently cancer metastasis. Protein-folding and cellular homeostasis are essential functions of the endoplasmic reticulum (ER). An overabundance of protein accumulation within the ER jeopardizes cellular homeostasis causing stress. Under ER stress, these functions fail to maintain cellular stability resulting in the activation of the unfolded protein response (UPR). The UPR allows the cell the capacity to overcome cellular instability through the IRE1š¯›¼, ATF6, and PERK sensor-driven pathways. It has been recently shown that the tumor necrosis factor alpha induced protein-8 type 1 (TNFAIP8L1) gene plays a role in tumor proliferation, although its participation within ER stress has not been established. By inducing cellular stress, we aim to characterize the effects of cellular stress and the associated pathways it uses to allow cancer metastasis. Similarly in yeast, cellular mechanism dysfunction affects the cellā€™s ability to maintain homeostasis and cell cycle activity. In Saccharomyces cerevisiae, complex molecular networks manage responses to extracellular stimulus and internal stresses simultaneously. Signaling pathways utilize internal switches such as g-proteins, which are conserved from yeast to human. We investigate how stress signaling and internal stress encourages cytokinetic defects. Pathway coordination of molecular machinery is an integral piece of genomic stability. The complete grasp of how these signaling pathways are regulated and their potentially unique contribution to medicine have yet to be discovered.

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