Culminating Project Title

SMURF1 as a Novel Regulator of PGC-1a

Date of Award

5-2016

Culminating Project Type

Thesis

Degree Name

Biological Sciences - Cell and Molecular: M.S.

Department

Biology

College

College of Science and Engineering

First Advisor

Dr. Brian L. Olson

Second Advisor

Dr. Timothy J. Schuh

Third Advisor

Dr. Latha Ramakrishnan

Creative Commons License

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

Abstract

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.

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