Differential role of the JNK and p38 MAPK pathway in c-Myc- and s-Myc-mediated apoptosis

The s-Myc is similar to c-Myc in its ability to induce apoptosis requiring caspase activation. However, s-Myc is distinct from c-Myc in that it has ac tivity to suppress tumor growth and does not require wild-type p53 to induc e apoptosis. These facts suggest differential regulation between s-Myc and c-Myc. Here we showed that s-Myc-mediated apoptosis triggered by UV was not inhibited by the inactive form mutant JNK (APF), though c-Myc-mediated apo ptosis was. Moreover, we found that JNK did not affect the transactivation activity of s-Myc, but stimulated that of c-Myc. In contrast, both Myc-medi ated apoptosis and caspase-3-like protease activation were suppressed by ki nase-negative MKK6 and an inactive form mutant p38(AGF). Our results indica te that s-Myc does not require the JNK signaling unlike c-Myc during UV-tri ggered apoptosis, but the MKK6/p38MAPK pathway might regulate common apopto tic machinery for both s-Myc and c-Myc upstream of caspase. (C) 2000 Academ ic Press.