Description
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Description : Apoptosis signal-regulating kinase 1 (ASK1), a MAP kinase kinase kinase, plays essential roles in stress-induced apoptosis . ASK1 is activated in response to a variety of stress-related stimuli through distinct mechanisms and activates MKK4 and MKK3, which in turn activate JNK and p38 . Overexpression of ASK1 activates JNK and p38 and induces apoptosis in several cell types through signals involving the mitochondrial cell death pathway. Embryonic fibroblasts or primary neurons derived from ASK1-/- mice are resistant to stress-induced JNK and p38 activation as well as cell death. Phosphorylation at Ser967 is essential for ASK1 association with 14-3-3 proteins and suppression of cell death . Oxidative stress induces dephosphorylation of Ser967 and phosphorylation of Thr845 in the activation loop of ASK1, both of which are correlated with ASK1 activity and ASK1-dependent apoptosis . Akt phosphorylates ASK1 at Ser83, which attenuates ASK1 activity and promotes cell survival.


