Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.25 (MEKK1)
 1,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase kinase kinase family, plays a critical role in mediating apoptosis signals initiated by a variety of death stimuli such as hydrogen peroxide and tumor necrosis factor-alpha. Owing to its critical role in inducing apoptosis, the activity of ASK1 is tightly regulated by various mechanisms such as post-translational modifications and protein-protein interactions. Here we describe the identification of G(1) to S phase transition protein 1 (GSPT1), which is associated with protein translation, as a regulator of ASK1. GSPT1 interacts with ASK1 and enhances ASK1-induced apoptotic activity through the activation of caspase-3. In vitro kinase assay data show that GSPT1 enhances ASK1 autophosphorylation and its kinase activity. Cell cycle-dependent GSPT1 induction and small interfering RNA analyses show that ASK1 autophosphorylation is dependent on the expression level of endogenous GSPT1 in cells. GSPT1 inhibits the binding of ASK1 to the 14-3-3 protein, an ASK1 inhibitor, while GSPT1 has no effect on the interaction between ASK1 and TRAF2, a C-terminal-binding activator of ASK1. Thus, our results reveal a novel role of GSPT1 in the regulation of ASK1-mediated apoptosis.
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PMID:G1 to S phase transition protein 1 induces apoptosis signal-regulating kinase 1 activation by dissociating 14-3-3 from ASK1. 1770 May 17