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.
From the Departments of Psychiatry and.
Carlos A
CA
Tristan
From the Departments of Psychiatry and.
Adriana
A
Ramos
From the Departments of Psychiatry and.
Neelam
N
Shahani
From the Departments of Psychiatry and.
Francesco E
FE
Emiliani
the Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka 599-8531, and.
Hidemitsu
H
Nakajima
Radiology and Radiological Science.
Christopher C
CC
Noeh
Radiology and Radiological Science, Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287.
Yoshinori
Y
Kato
the Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka 599-8531, and.
Tadayoshi
T
Takeuchi
the Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-8654, Japan.
Takuya
T
Noguchi
the Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-8654, Japan.
Hisae
H
Kadowaki
From the Departments of Psychiatry and.
Thomas W
TW
Sedlak
From the Departments of Psychiatry and.
Koko
K
Ishizuka
the Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-8654, Japan.
Hidenori
H
Ichijo
From the Departments of Psychiatry and Neuroscience, asawa1@jhmi.edu.
Akira
A
Sawa
D000595:Amino Acid Sequence; D001665:Binding Sites; D005786:Gene Expression Regulation; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000098563:Seven in Absentia Proteins
D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D006861:Hydrogen Peroxide; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human
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)