INDUCTION OF APOPTOSIS BY THE C-MYC HELIX-LOOP HELIX LEUCINE ZIPPER DOMAIN IN MOUSE 3T3-L1 FIBROBLASTS/

The cellular proto-oncogene c-myc is involved in cell proliferation an d transformation but is also implicated in the induction of programmed cell death (apoptosis). The c-Myc protein is a transcriptional activa tor with a carboxyl-terminal basic region/helix-loop-helix (HLH)/leuci ne zipper (LZ) domain. It forms heterodimers with the HLH/LZ protein M ax and transactivates gene expression after binding DNA E-box elements . We have studied the phenotype of dominant negative mutants of c-Myc and Max in microinjection experiments. Max mutants with a deleted or m utated basic region inhibited DNA synthesis in serum stimulated 3T3-L1 mouse fibroblasts. In contrast, mutants of c-Myc expressing only the basic reson/HLH/LZ or HLH/LZ domains rapidly induced apoptosis at low and high serum levels. Co expression of the HLH/LZ domains of c-Myc an d Max failed to do so. We suggest that the c-Myc HLH/LZ domain induces apoptosis by specific interaction with cellular factors different to Max.