Abstract
The expression of c-myc promotes cell proliferation and also sensitizes cells to various extracellular apoptotic stimuli. However, signal pathways regulating the function of Myc proteins during apoptosis are unknown. c-Jun N-terminal kinase (JNK) is activated by various apoptotic stimuli, but neither the target molecule(s) or the action of JNK has been identified in Myc-mediated apoptosis. Here, we found that JNK selectively interacted with, and phosphorylated, c-Myc at Ser-62 and Ser-71 as confirmed with phospho-c- Myc-specific antibodies. Interestingly, dominant negative mutant JNK(APF) impaired the c-Myc-dependent apoptosis, but not mutated c-Myc (S62A/S71A)- dependent apoptosis triggered by UV irradiation. Furthermore, c-Myc (S62A/S71A)-expressing NIH3T3 cells were not sensitized like wild type c-Myc- expressing NIH3T3 cells to JNK-activating apoptotic stimuli, such as UV and Taxol. These results indicate that the JNK pathway is selectively involved in the c-Myc-mediated apoptosis and that the apoptotic function of c-Myc is directly regulated by JNK pathway through phosphorylation at Ser-62 and Ser- 71.
| Original language | English |
|---|---|
| Pages (from-to) | 32580-32587 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 274 |
| Issue number | 46 |
| DOIs | |
| Publication status | Published - 1999 Nov 12 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Biochemistry
Cite this
Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c- Jun N-terminal kinase. / Noguchi, Kohji; Kitanaka, Chifumi; Yamana, Hironobu; Kokubu, Akiko; Mochizuki, Toshihiro; Kuchino, Yoshiyuki.
In: Journal of Biological Chemistry, Vol. 274, No. 46, 12.11.1999, p. 32580-32587.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c- Jun N-terminal kinase
AU - Noguchi, Kohji
AU - Kitanaka, Chifumi
AU - Yamana, Hironobu
AU - Kokubu, Akiko
AU - Mochizuki, Toshihiro
AU - Kuchino, Yoshiyuki
PY - 1999/11/12
Y1 - 1999/11/12
N2 - The expression of c-myc promotes cell proliferation and also sensitizes cells to various extracellular apoptotic stimuli. However, signal pathways regulating the function of Myc proteins during apoptosis are unknown. c-Jun N-terminal kinase (JNK) is activated by various apoptotic stimuli, but neither the target molecule(s) or the action of JNK has been identified in Myc-mediated apoptosis. Here, we found that JNK selectively interacted with, and phosphorylated, c-Myc at Ser-62 and Ser-71 as confirmed with phospho-c- Myc-specific antibodies. Interestingly, dominant negative mutant JNK(APF) impaired the c-Myc-dependent apoptosis, but not mutated c-Myc (S62A/S71A)- dependent apoptosis triggered by UV irradiation. Furthermore, c-Myc (S62A/S71A)-expressing NIH3T3 cells were not sensitized like wild type c-Myc- expressing NIH3T3 cells to JNK-activating apoptotic stimuli, such as UV and Taxol. These results indicate that the JNK pathway is selectively involved in the c-Myc-mediated apoptosis and that the apoptotic function of c-Myc is directly regulated by JNK pathway through phosphorylation at Ser-62 and Ser- 71.
AB - The expression of c-myc promotes cell proliferation and also sensitizes cells to various extracellular apoptotic stimuli. However, signal pathways regulating the function of Myc proteins during apoptosis are unknown. c-Jun N-terminal kinase (JNK) is activated by various apoptotic stimuli, but neither the target molecule(s) or the action of JNK has been identified in Myc-mediated apoptosis. Here, we found that JNK selectively interacted with, and phosphorylated, c-Myc at Ser-62 and Ser-71 as confirmed with phospho-c- Myc-specific antibodies. Interestingly, dominant negative mutant JNK(APF) impaired the c-Myc-dependent apoptosis, but not mutated c-Myc (S62A/S71A)- dependent apoptosis triggered by UV irradiation. Furthermore, c-Myc (S62A/S71A)-expressing NIH3T3 cells were not sensitized like wild type c-Myc- expressing NIH3T3 cells to JNK-activating apoptotic stimuli, such as UV and Taxol. These results indicate that the JNK pathway is selectively involved in the c-Myc-mediated apoptosis and that the apoptotic function of c-Myc is directly regulated by JNK pathway through phosphorylation at Ser-62 and Ser- 71.
UR - http://www.scopus.com/inward/record.url?scp=0032703216&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032703216&partnerID=8YFLogxK
U2 - 10.1074/jbc.274.46.32580
DO - 10.1074/jbc.274.46.32580
M3 - Article
C2 - 10551811
AN - SCOPUS:0032703216
VL - 274
SP - 32580
EP - 32587
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 46
ER -