Student Author(s)

Katherine Lane, Hope College

Faculty Mentor(s)

Dr. Leah Chase, Biology and Chemisty

Document Type


Event Date



System xc- is involved in transporting cystine into cells and glutamate out of cells, and ultimately in production of the antioxidant glutathione. Antioxidants are important in protecting cells from oxidative stress which can occur when waste products like H2O2 build up in the cell. Previous studies have shown that a critical regulator mTORC regulates system xc- by phosphorylating serine 26 (S26) on the N-terminus of the cystine/glutamate antiporter xCT, leading to a reduction in transport activity. The specific objective of this study is to determine the mechanism by which phosphorylation of S26 affects activity. To address this question, we used site-directed mutagenesis to create two mutants, one in which S26 was changed to alanine (S26A) and one in which S26 was changed to aspartate (D). S26A is unable to be phosphorylated because it is lacking a hydroxyl group on its sidechain, and S26D is a phosphomimetic, as aspartate is similar in size and charge to a phosphorylated serine. We are currently expressing these two mutants of xCT in COS-7 cells to determine how these mutants alter the cell surface expression of the antiporter. In addition, we are evaluating whether these mutations impact the post-translational modification of the transporter at another site, given that mTORC is commonly upregulated. Ultimately this work will allow us to understand the specific mechanism by which S26 phosphorylation and the mTORC pathway regulate transporter activity.


This research was supported by the A. Paul and Carol Schaap Undergraduate Research Fund and the De Vries Summer Research Fund.