ASK1-Signaling promotes c-Myc protein stability during apoptosis

We previously reported that JNK is involved in the regulation of c-Myc-medi ated apoptosis triggered by UV irradiation and anticancer drug treatment. H ere 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 r egulation of protein stability and function of c-Myc. The ASK1 JNK pathway enhanced the protein stability of c-Myc through phosphorylation at Ser-62 a nd Ser-71, which was required for c-Myc-dependent apoptosis by ASK1-signali ng. Interestingly, ASK1-signaling attenuated the degradation of ubiquitinat ed c-Myc without affecting the ubiquitination process. Together, these find ings indicate that the ASK1-JNK pathway promotes the proapoptotic activity of c-Myc by modulating c-Myc protein stability through phosphorylation at S er-62 and Ser-71. (C) 2001 Academic Press.