Sponsor
Portland State University. Department of Biology
First Advisor
Jeffrey Singer
Date of Publication
Summer 8-2-2017
Document Type
Dissertation
Degree Name
Doctor of Philosophy (Ph.D.) in Biology
Department
Biology
Language
English
Subjects
Ubiquitin, Cyclins, Cell cycle -- Regulation
DOI
10.15760/etd.5666
Physical Description
1 online resource (xvii, 142 pages)
Abstract
Cul3 forms E3 ubiquitin ligase complexes that regulate a variety of cellular processes. This dissertation describes Cul3's role in several of these pathways and provides new mechanistic details regarding the role of Cul3 in eukaryotic cells. Cyclin E is an example of a protein that is regulated in a Cul3-dependent manner. Cyclin E is a cell cycle regulator that controls the beginning of DNA replication in mammalian cells. Increased levels of cyclin E are found in some cancers, in addition, proteolytic removal of the cyclin E N-terminus occurs in some cancers and is associated with tumorigenesis. Cyclin E levels are tightly regulated and controlled in part through ubiquitin-mediated degradation initiated by one of two E3 ligase complexes, Cul1 and Cul3. Cul1 mediated degradation of cyclin E is triggered by cyclin E phosphorylation, however the mechanism Cul3 uses to ubiquitinate cyclin E is poorly understood. In order to gain a better understanding of how Cul3 mediates cyclin E destruction we identified the degron on cyclin E that is important in Cul3 dependent degradation. In addition, we show this degron is lacking in LMW cyclin E (found in abundance in breast cancer), providing a novel mechanism for how these cyclin E modifications result in increased cyclin E levels by avoiding the Cul3 degradation pathway.
Rights
In Copyright. URI: http://rightsstatements.org/vocab/InC/1.0/ This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
Persistent Identifier
http://archives.pdx.edu/ds/psu/21214
Recommended Citation
Davidge, Brittney Marie, "The Cul3 Ubiquitin Ligase: an Essential Regulator of Diverse Cellular Processes" (2017). Dissertations and Theses. Paper 3782.
https://doi.org/10.15760/etd.5666