| Summary: | 碩士 === 國立中興大學 === 生命科學系所 === 103 === Abstract
Peptidylarginine deiminase type 2 (PADI2) is a post-translational modification enzyme that catalyzes arginine residues into the citrulline residues. Previous studies have shown that PADI2 promotes protein citrullinations in lymphocytes and it might play an important role in inflammation. We found that overexpression of PADI2 promotes apoptosis in activated T cells previously. Whether PADI2 participate in the pathway of activated T cell autonomous death (ACAD) is still curious. In the delicate PADI2-mediated ACAD, we found that overexpression of PADI2 displayed higher levels of citrullinated protein which induced the ER stress significantly. The high levels of citrullinated protein results in unfolding protein response (UPR) of ER stress and increases the loading of protein degradation. Autophagy could cause degradation of the citrullinated and unfolding protein. Herein, PADI2 could enhance autophagy in Jurkat T cells and lead to a degradation of p62 and the accumulation of LC3-II. Autophagy and apoptosis are two critical mechanisms which participate against cellular stress, cell activation, survival and homeostasis. PADI2-overexpressed Jurkat T cells caused the activation of Th17 cells to increase mRNA expression of cytokines, such as IL-17, IL-21, IL-22 and TNF. Cytokines provoked caspase expression and led to caspase-mediated cleavage of Beclin-1 which was an important factor of apoptotic signaling. Knockdown of BCEN1 rescued cell survival due to the increase of Bcl-xL and the decrease of caspase-3. We suggested that PADI2 participated in the activated T cell-induced autonomous death through triggering ER stress pathway, stimulating the expression of cytokines and promoting autophagy by PADI2-citrullinated protein.
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