Honors College Thesis
 

The Effect of Protein Nitration on Cell Survival Pathways in Schwann Cells

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https://ir.library.oregonstate.edu/concern/honors_college_theses/9g54xr287

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  • Neurofibromatosis type 2 (NF2) is a genetic disorder caused by the inactivation of the merlin tumor suppressor gene. NF2 patients develop bilateral vestibular schwannomas (VS) and other nervous system tumors with no effective drug treatment option. In pathological conditions, including NF2, production of the oxidant peroxynitrite leads to protein tyrosine nitration. While tyrosine nitration is seen in multiple tumor types, its role in tumorigenesis is unknown, although we have discovered that prevention of tyrosine nitration selectively decreased merlin deficient (MD) Schwann cell survival. This research is the first focused effort to determine the signaling pathways regulated by tyrosine nitration in pathological conditions. Immunoprecipitations followed by mass spectrometry analysis identified proteins endogenously nitrated in VS from NF2 patients, and in human MD-Schwann cells. Then we performed phosphorylation arrays for receptor tyrosine kinases (RTKs), and phospho-kinases, to characterize the relationship between nitrated proteins and survival pathway activation. While RTKs were unaffected, the phospho-MAPK arrays demonstrated a role of nitration in supporting survival pathway activation in MD-Schwann cells, including the PI3K/Akt pathway, and the MEK/ERK pathway. The identification of specific nitrated proteins that promote schwannoma growth could provide novel targets for the treatment of NF2 and possibly other nervous system tumors as well.
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  • Intellectual Property (patent, etc.)
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  • 2021-06-04 to 2023-07-05

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