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J Biol Chem. 2015 Jan 2;290(1):56-64. doi: 10.1074/jbc.M114.596205. Epub 2014 Nov 12.

Role of apoptosis signal-regulating kinase 1 (ASK1) as an activator of the GAPDH-Siah1 stress-signaling cascade.

Author information

1
From the Departments of Psychiatry and.
2
the Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka 599-8531, and.
3
Radiology and Radiological Science.
4
Radiology and Radiological Science, Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287.
5
the Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-8654, Japan.
6
From the Departments of Psychiatry and Neuroscience, asawa1@jhmi.edu.

Abstract

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays roles in both energy maintenance, and stress signaling by forming a protein complex with seven in absentia homolog 1 (Siah1). Mechanisms to coordinate its glycolytic and stress cascades are likely to be very important for survival and homeostatic control of any living organism. Here we report that apoptosis signal-regulating kinase 1 (ASK1), a representative stress kinase, interacts with both GAPDH and Siah1 and is likely able to phosphorylate Siah1 at specific amino acid residues (Thr-70/Thr-74 and Thr-235/Thr-239). Phosphorylation of Siah1 by ASK1 triggers GAPDH-Siah1 stress signaling and activates a key downstream target, p300 acetyltransferase in the nucleus. This novel mechanism, together with the established S-nitrosylation/oxidation of GAPDH at Cys-150, provides evidence of how the stress signaling involving GAPDH is finely regulated. In addition, the present results imply crosstalk between the ASK1 and GAPDH-Siah1 stress cascades.

KEYWORDS:

Apoptosis Signal-regulating Kinase 1 (ASK1); Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH); Nuclear Translocation; Oxidative Stress; Protein Phosphorylation; Protein Translocation; Protein-Protein Interaction; Seven in absentia homolog 1 (Siah1)

PMID:
25391652
PMCID:
PMC4281757
DOI:
10.1074/jbc.M114.596205
[Indexed for MEDLINE]
Free PMC Article

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