TY - JOUR
T1 - ASK1-signaling promotes c-Myc protein stability during apoptosis
AU - Noguchi, Kohji
AU - Kokubu, Akiko
AU - Kitanaka, Chifumi
AU - Ichijo, Hidenori
AU - Kuchino, Yoshiyuki
N1 - Funding Information:
We thank Drs. A. Tomida, H. Seimiya, N. Fujita, T. Mashima, and Z. Chen for providing reagents and valuable suggestions. This work was supported by grants from the Ministry of Education, Science, Sports, and Culture of Japan for Cancer Research (to K.N. and to Y.K.) and in part by a Grant-in-Aid from the Ministry of Health and Welfare of Japan for the Second-Term Comprehensive 10-Year Strategy for Cancer Control (to Y.K.).
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1006/bbrc.2001.4498
DO - 10.1006/bbrc.2001.4498
M3 - Article
C2 - 11243879
AN - SCOPUS:0034805077
VL - 281
SP - 1313
EP - 1320
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 5
ER -