Date of Award

8-1-2022

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Biological Sciences

Content Description

1 online resource (vi, 172 pages) : illustrations (some color)

Dissertation/Thesis Chair

Morgan A Sammons

Committee Members

ChangHwan Lee, Cara Pager, Andy Berglund, Andre Melendez

Keywords

p53 antioncogene, Cancer, Gene regulatory networks, Stress (Physiology)

Subject Categories

Biology | Cell Biology | Molecular Biology

Abstract

The transcription factor, p53, plays a pivotal role in the oversight of many stimulus-dependent pathways. Its ability to respond to a wide variety of cellular stress stimuli by activating a broad range of target genes has led it to be characterized as a stress-dependent transcription factor. Our research focuses on deconvoluting the varied transcriptional response to distinct stress signals in an attempt to define the regulatory strategies leading to gene activation after cell stress. We have found that distinct stress response networks, some of which are p53-independent, are converging at activation of a common set of target genes. Our data suggest that Activating Transcription Factor 3 (ATF3), is a p53 target gene that is induced by multiple stress-dependent networks. We hypothesize that a group of direct and canonical p53 target genes are being activated in a p53-independent manner in response to other environmental conditions. We propose that the regulation of these p53 target genes is being achieved by the binding of stress-dependent transcription factors other than p53, at distinct regulatory regions such as enhancers and promoters. Researching the mechanisms of target gene activation induced by these parallel, stress-dependent pathways will provide insight into the regulatory paradigms employed by organisms to maintain and repair cellular homeostasis. Comparing and contrasting the transcriptional response to a variety of cellular stresses will allow for a better understanding of the general mechanisms used by the cell to respond to the vast array of environmental insults, which will provide insight into putative targets that may be attractive for future anticancer therapies.

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