Mapping the reactive oxygen species mediated cysteine modification patterns on ATG4B
Date Issued
2011
Date
2011
Author(s)
Chiu, Hsien-I
Abstract
Autophagy is a large-scale metabolic pathway to degrade cytosolic substances in eukaryotes, it controls the balance of cytosolic materials. Recent studies pointed out that autophagy is closely related to various diseases and physiological processes such as cancer, neurodegeneration, innate & adaptive immunity, ageing, development and cell death, etc. It has been shown that autophagy and ROS signals are inextricable linked. Many studies emphasized on changes in autophagy induced by ROS, whereas only few studies focused on whether ROS-induced ATG proteins’ post-transcriptional modifications would affect these proteins’ functions.
A preliminary study showed that ATG4A could be oxidized by H2O2 and lost its enzyme activity, But, it could be reduced and regain its function. Since the regulatory mechanism of other ATG4 family proteins is still unclear, we attempt to establish a MS based analysis method to monitor ROS-mediated post-transcriptional modifications on ATG4B, and further elucidate the relationships between these PTM and ATG4B’s activity. We first treated ATG4B with different concentration of H2O2 to simulate ROS-mediated Cys oxidation and found that ATG4B is more sensitive to ROS than ATG4A. Also, we perform differential alkylation labeling to demarcate various oxidation states of ATG4B’s Cys. The analysis by mass spectrometry suggests that Cys 78 and Cys 189 on ATG4B are the ROS sensor which regulate ATG4B’s activity.
Subjects
autophagy
PTM
differential alkylation labeling
SDGs
Type
thesis
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