S-Glutathionylation: Indicator of Cell Stress and Regulator of the Unfolded Protein Response

The interplay of protein phosphorylation and protein S-glutathionylation pathways in cell signaling. Under oxidative/nitrosative stress (indicated by ROS/ RNS), pi GST monomers associate with the target proteins c-Jun, JNK, and TRAF2, which are consequently S-glutathionylated (as indicated by –SSG). The immediate effect of S-glutathionylation could be TRAF2 activation, as well as the phosphorylative activation (indicated by –P) of c-Jun and JNK, culminating in the deployment of apoptotic or proliferative pathways. In addition, S-glutathionylation of pi GST results in its aggregation and concomitant inactivation. Dashed lines and arrows indicate hypothetical, rather than experimentally established, steps.