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

Carlos A. Tristan, Adriana Ramos, Neelam Shahani, Francesco E. Emiliani, Hidemitsu Nakajima, Christopher C. Noeh, Yoshinori Kato, Tadayoshi Takeuchi, Takuya Noguchi, Hisae Kadowaki, Thomas W. Sedlak, Koko Ishizuka, Hidenori Ichijo, Akira Sawa

研究成果: Article査読

13 被引用数 (Scopus)

抄録

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 GAPDHSiah1 stress cascades.

本文言語English
ページ(範囲)56-64
ページ数9
ジャーナルJournal of Biological Chemistry
290
1
DOI
出版ステータスPublished - 2015 1 2
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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