Protein arginine methylation. The guardian of cell survival: The role of PRMT1 in cell viability
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Protein arginine methylation is a common posttranslational modification in eukaryotes that can affect many cellular functions such as transcription, cell differentiation and lymphocyte signaling. In my study, I demonstrate that overexpression of an inactive form of protein arginine methyltransferase 1 (PRMT1) inhibits nerve growth factor (NGF) stimulated neurite outgrowth of PC12 cells, and induces cell loss both in PC12 cells and non-neuronal HEK 293 cells. Overexpression of wild type PRMT1 improves cell viability against apoptosis stimuli such as DNA damage or oxidative stress. Cell loss induced by overexpression of the inactive form of PRMT1 involves the inhibition of NF-κB activity. ShRNA-mediated knockdown of PRMT1 also induces cell loss; however, it involves a different mechanism since the activity of NF-κB is not affected. Neither overexpression of the inactive form of PRMT1 nor knockdown of PRMT1 affects cell proliferation, which confirms that cell death is the major contribution to cell loss and is consistent with the results from cell viability experiments and morphology studies. Cell death induced by overexpression of the inactive form of PRMT1 and knockdown of PRMT1 involves both caspase-dependent and caspase-independent pathways. However, it is not a typical cell apoptosis since caspase 3 is not activated and DNA fragmentation is absent. My study is the first to directly demonstrate the importance of PRMT1 and protein arginine methylation in cell viability of adult mammalian cells such as PC12 cells and HEK 293 cells.