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

Biochem Biophys Res Commun. 2000 Jan 7;267(1):221-7. doi: 10.1006/bbrc.1999.1952.

Abstract

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 activity to suppress tumor growth and does not require wild-type p53 to induce 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 apoptosis 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-mediated apoptosis and caspase-3-like protease activation were suppressed by kinase-negative MKK6 and an inactive form mutant p38(AGF). Our results indicate that s-Myc does not require the JNK signaling unlike c-Myc during UV-triggered apoptosis, but the MKK6/p38MAPK pathway might regulate common apoptotic machinery for both s-Myc and c-Myc upstream of caspase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Apoptosis / radiation effects
  • COS Cells
  • Calcium-Calmodulin-Dependent Protein Kinases*
  • Caspases / metabolism
  • Cell Line
  • Chloramphenicol O-Acetyltransferase / genetics
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Kinetics
  • MAP Kinase Kinase 6
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Mitogen-Activated Protein Kinases / metabolism*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Rats
  • Recombinant Proteins / metabolism
  • Transfection
  • Ultraviolet Rays
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Proto-Oncogene Proteins c-myc
  • Recombinant Proteins
  • Chloramphenicol O-Acetyltransferase
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 6
  • MAP2K6 protein, human
  • Mitogen-Activated Protein Kinase Kinases
  • Caspases