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Redox modification of Fes1 and its role in cellular oxidative stress response
Author(s) -
Nicklow Erin,
Sevier Carolyn
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.604.7
Subject(s) - oxidative stress , reactive oxygen species , cytosol , microbiology and biotechnology , heat shock protein , chemistry , protein aggregation , oxidative phosphorylation , biochemistry , chaperone (clinical) , biology , enzyme , medicine , gene , pathology
Elevated levels of reactive oxygen species (ROS) are associated with many degenerative disorders (like aging, Alzheimer's, atherosclerosis, and diabetes). Increased cellular ROS levels correlate with accumulation of irreversibly oxidized proteins, which are prone to misfolding and aggregation. 70‐kDa heat shock proteins (Hsp70s) are a conserved family of ATPases that serve as molecular chaperones to refold misfolded and aggregated proteins, such as those damaged by ROS. As such, Hsp70s play a critical role in protein quality control under oxidative stress. To examine the role of cytosolic Hsp70s in coping with oxidative stress, I screened S. cerevisiae strains mutated for each of the chaperones and their cofactors for peroxide sensitivity. Notably, I found that the nucleotide exchange factor Fes1 is required for cell survival during oxidative stress, and that when cells are grown in medium containing peroxide, Fes1 is modified directly by ROS. Preliminary data suggest that this oxidative modification of Fes1 alters its activity, which I hypothesize confers a protective role during stress conditions and allows cells to sense and respond to elevated ROS levels. I am currently focused on characterizing this event to determine how Fes1 is modified by ROS and how modification affects Fes1's protein quality control activities in the cell.