Ectopic expression of CHOP (GADD153) induces apoptosis in M1 myeloblastic leukemia cells.

CHOP (GADD153) is a member of the C/EBP family and a stress-induced protein. To investigate the role of CHOP in cellular growth, we expressed CHOP conditionally in M1 myeloblastic leukemia cells that do not express p53 protein. More than 60% of M1 cells died through apoptosis 72 h after CHOP induction. Site-directed mutagenesis revealed that this process requires leucine zipper domain but neither intact basic region nor trans-activation domain. CHOP-mediated apoptosis accompanied downregulation of bcl-2 mRNA and overexpression of Bcl-2 delayed the process. Our results indicate that CHOP can induce apoptosis in a p53-independent manner.