Fig. 5.

Schema flowchart illustrating the role of HSP90α in the mechanisms of cellular survival. HSP90α induction in response to environmental pollutant-mediated oxidative stress promotes the activation of its client proteins such as STATs of the JAK/STAT pathway, ERK1/2 of the Ras/Raf/MAPK pathway, and Akt of the PI3K pathway. STATs upon activation during HSP90α induction favor survival after translocation to the nucleus. ERK1/2 and Akt activations under similar conditions promote cellular survival via their downstream effectors like Elk-1 activations and Bcl-2 upregulation, respectively. Activation of NF-κB by both the survival kinases also provides anti-apoptotic effect facilitating cellular survival. HSP90α-mediated Akt activation at the same time also acts to downregulate ASK1 allowing inhibition of ASK1-mediated JNK1/2 apoptotic signaling. Thus, HSP90α by modulating a series of signaling cascades protects against apoptosis and promotes hepatocyte survival