THE S-MYC PROTEIN HAVING THE ABILITY TO INDUCE APOPTOSIS IS SELECTIVELY EXPRESSED IN RAT EMBRYO CHONDROCYTES

Gene transfection experiments demonstrated that overexpression of the s-myc gene under the control of a human metallothionein promoter induc ed apoptosis in cells such as rat and human glioma cells. In contrast to c-Myc-mediated apoptosis requiring withdrawal of serum growth facto rs, s-myc expression induced apoptosis in glioma cells in the presence of 10% fetal calf serum. Whereas, s-Myc-mediated apoptosis was suppre ssed in proportion to the increase of bcl-2 expression as seen in c-My c mediated apoptosis. The s-myc gene was expressed in rat embryo cells being committed to differentiate to hypertrophic chondrocytes which u ndergo programmed cell death. CAT assay demonstrated that in the NH,te rminal region, the s-Myc protein contains a domain structure required for expression of transactivation activity that is approximately six t imes higher than that of c-Myc. Therefore, these findings strongly sug gest that s-Myc may play an important role in transcription regulation of a set of genes whose expression induces programmed cell death in v itro and in vivo.