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

Oncogene volume 27, pages 1297–1305 (2008)Cite this article

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.

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Acknowledgements

We thank Dr Hidenori Ichijo for HA-ASK1 and ASK1K709R expression plasmids. This work was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (01-PJ10-PG6-01GN16-0005) (to SC) and by MOCIE grants from Intelligence Bioinformatics and Application Center (TGW0200513), KRIBB (to BP).

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Authors and Affiliations

  1. College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea

    J A Lee & S Cho

  2. Research Institute for Translational System Biomics, Chung-Ang University, Seoul, Republic of Korea

    J A Lee & S Cho

  3. Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejon, Republic of Korea

    J E Park, D H Lee, S G Park & B C Park

  4. College of Pharmacy, Chungnam National University, Daejon, Republic of Korea

    P K Myung

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  1. J A Lee
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Correspondence to B C Park or S Cho.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Lee, J., Park, J., Lee, D. et al. G1 to S phase transition protein 1 induces apoptosis signal-regulating kinase 1 activation by dissociating 14-3-3 from ASK1. Oncogene 27, 1297–1305 (2008). https://doi.org/10.1038/sj.onc.1210740

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