Role of apoptosis signal-regulating kinase 1 (ASK1) as an activator of the GAPDH-Siah1 stress-signaling cascade.
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.
Mesh Terms:
Amino Acid Sequence, Binding Sites, Gene Expression Regulation, Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating), HEK293 Cells, Humans, Hydrogen Peroxide, MAP Kinase Kinase Kinase 5, Molecular Sequence Data, Nuclear Proteins, Oxidative Stress, Phosphorylation, Protein Binding, Recombinant Fusion Proteins, Signal Transduction, Ubiquitin-Protein Ligases
Amino Acid Sequence, Binding Sites, Gene Expression Regulation, Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating), HEK293 Cells, Humans, Hydrogen Peroxide, MAP Kinase Kinase Kinase 5, Molecular Sequence Data, Nuclear Proteins, Oxidative Stress, Phosphorylation, Protein Binding, Recombinant Fusion Proteins, Signal Transduction, Ubiquitin-Protein Ligases
J. Biol. Chem.
Date: Jan. 02, 2015
PubMed ID: 25391652
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