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dc.contributor.advisorSevier, Carolyn
dc.contributor.authorXu, Mengni
dc.description.abstractRecently, it has been shown that oxidative protein folding in the endoplasmic reticulum (ER) produces potentially significant amounts of cellular reactive oxygen species (ROS). Although ROS accumulation can cause profound damage to the cell through a phenomenon called oxidative stress, ROS have also recently been shown to be fundamental components of many protective signaling pathways in the ER that respond and prevent oxidant-induced damage. However, many questions regarding how cells protect against ER-derived oxidative stress still remain. Here, we report further evidence of a new role for the well-characterized Hsp70 ER molecular chaperone BiP as a sensor of ROS imbalance in the ER. Previously, the lab has shown that BiP’s conserved cysteine is directly modified by ROS during stress and that this modification not only protects cells from oxidative stress, but also results in a loss of its ATPase activity. In order to better assess the impact of BiP cysteine modification on BiP function, we created and characterized mutant alleles that could possibly mimic the protecting feature of BiP’s modified cysteine by substituting BiP’s conserved cysteine with all 19 other amino acids. Our results show that when BiP’s conserved cysteine is substituted with charged or bulky residues, BiP not only protects cells under conditions of stress, but also triggers heightened unfolded protein response (UPR), decreased protein translocation into the ER, and prevents protein aggregation. We propose that under conditions of oxidative stress, BiP, modified by ROS, alters its activities in ways that protect cells from excess stress through loss of its ATPase and normal chaperone functions.
dc.subjectBiological sciences honors program; nill
dc.titleMutagenesis of a conserved cysteine in the Hsp70 molecular chaperone BiP: Impact of amino acid substitution on BiP’s ability to protect cells against endoplasmic reticulumderived oxidative stress
dc.typedissertation or thesis Sciences of Arts of Biological Sciences

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