Date of Award
Culminating Project Type
Biological Sciences - Cell and Molecular: M.S.
College of Science and Engineering
Dr. Brian L. Olson
Dr. Timothy J. Schuh
Dr. Latha Ramakrishnan
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Keywords and Subject Headings
SMURF1 CRISPR siRNA PGC-1 Parkinson's Regulator
Parkinson’s disease is a neurodegenerative disorder caused by the impairment and/or death of the dopaminergic neurons in the area of the brain that controls movement, and is diagnosed in roughly 60,000 Americans each year. Low levels of the protein PGC-1α have been linked to this disease, but efforts to find a chemical that causes higher production of PGC-1α. Therefore, the focus must change to determining whether or not it is possible to reduce the degradation of PGC-1α without impacting the production rate of PGC-1α, thereby increasing PGC-1α levels. Prior studies have shown that the protein CDC4 causes PGC-1α to be degraded through ubiquitination, which could make CDC4 a possible target for deletion in order to increase PGC-1α levels. However, CDC4 is a tumor suppressor gene, making it a poor target for deletion, as this could cause other problems for the patient. As a result, it has been deemed necessary to find another ubiquitin ligase protein that also happens to be an oncogene, as this would not cause as many side effects for a patient if this were deleted. Initial studies have shown that the protein SMURF1 may be a ubiquitin ligase which targets PGC-1α for degradation, and it is likely an oncogene. This is believed to be the case because an increase in SMURF1 levels in cells causes a decrease in the levels of PGC-1α within these same cells. However, it is possible that this effect is due to an increase in SMURF1 levels causing a change in the physiology of cells or some other nonspecific effect. Therefore, the next step in this study will be to determine whether or not PGC-1α and SMURF1 bind directly to each other through co-immunoprecipitation experiments.
Fogarty, Stuart A., "SMURF1 as a Novel Regulator of PGC-1a" (2016). Culminating Projects in Biology. 9.