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Title 

G1 to S phase transition protein 1 induces apoptosis signal-regulating kinase 1 activation by dissociating 14-3-3 from ASK1

Authors 

J A LeeJ E ParkDo Hee LeeSung Goo ParkP K MyungByoung Chul ParkS Cho

Publisher 

Nature Publishing Group

Issue Date 

2008

Citation 

Oncogene, vol. 27, no. 9, pp. 1297-1305

Keywords 

apoptosisapoptosis signal-regulating kinase 1G1 to S phase transition 1Mitogen-activated protein kinaseapoptosis signal regulating kinase 1g1 to s phase transition protein 1proteinsmall interfering RNAtumor necrosis factor alphatumor necrosis factor receptor associated factor 2

Abstract 

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-α. 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 G1 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.

ISSN 

0950-9232

Link 

http://dx.doi.org/10.1038/sj.onc.1210740

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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