ASK1-signaling promotes c-Myc protein stability during apoptosis.
We previously reported that JNK is involved in the regulation of c-Myc-mediated apoptosis triggered by UV irradiation and anticancer drug treatment. Here we show that ASK1 is an upstream regulator for c-Myc-mediated apoptosis triggered by UV, and we found a direct role for Ser-62 and Ser-71 in the regulation of protein stability and function of c-Myc. The ASK1-JNK pathway enhanced the protein stability of c-Myc through phosphorylation at Ser-62 and Ser-71, which was required for c-Myc-dependent apoptosis by ASK1-signaling. Interestingly, ASK1-signaling attenuated the degradation of ubiquitinated c-Myc without affecting the ubiquitination process. Together, these findings indicate that the ASK1-JNK pathway promotes the proapoptotic activity of c-Myc by modulating c-Myc protein stability through phosphorylation at Ser-62 and Ser-71.
Noguchi
K
K
Department of Bioactive Molecules, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan. knoguchi@nih.go.jp
Kokubu
A
A
Kitanaka
C
C
Ichijo
H
H
Kuchino
Y
Y
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D029681:Arabidopsis Proteins; D006801:Humans; D007700:Kinetics; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D010940:Plant Proteins / Q000235:genetics / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D014452:Ubiquitins / Q000378:metabolism
C120363:ASK1 protein, Arabidopsis; D029681:Arabidopsis Proteins; D010940:Plant Proteins; D016271:Proto-Oncogene Proteins c-myc; D014452:Ubiquitins; D010768:Phosphoserine; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases