April Choi L&S Sciences
The Mechanism of Nor-1 Mitochondrial Translocation during Thymocyte Negative Selection
Nor-1 is a protein that can promote death of CD4+ CD8+ double positive thymocytes, cells in the process of maturing into T cells. In the thymus, these double positive thymocytes undergo a process called negative selection, in which any thymocytes that recognize self-molecules that our own body produces are killed. This makes sure that our body mounts an immune response when it encounters a foreign pathogen. Failure during this negative process results in autoimmune diseases such as systemic lupus erythematosus (the go-to disease whenever someone is sick in the episodes of House), Graves’ disease and rheumatoid arthritis. Presently, the exact molecular mechanism of negative selection is poorly understood. Nor-1 can induce apoptosis (cell death) by assisting in translations of new proteins, but it can also promote cell death by moving into the mitochondria and turning on Bcl-2 into a pro-apoptotic molecule by exposing its killer BH3 domain1. The mechanism for inducing Nor-1 movement remains unclear. Additionally, the relative importance of the transcriptional versus mitochondrial Nor-1 killing mechanisms is unknown. I hope to identify the portion of the protein necessary for mitochondrial translocation (Nor-1 movement) by creating mutant Nor-1 proteins and seeing where these proteins end up within the cell. I will also compare the relative importance of transcription-dependent and mitochondrial killing.
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