Md-i, a Member of the Bcl-2 Family, Delays Apoptosis Induced by c-Myc Overexpression in Chinese Hamster Ovary Cells1

McI-i, a protein increased early in the differentiation of human myelo blastic ML-! cells, has sequence Similarityto Bcl-2. In the present study, we determined whether Md-i has functional similarity to Bcl-2 by testing its ability to inhibit apoptosis induced by c-Myc overexpression. This was carried out using Chinese hamster ovary 5AHSmyc cells which contain the human c-myc proto-oncogene under the control of a heat shock promoter. Heat treatment induces c-Myc overexpression and thus apop tosis as determined by internucleosomal DNA fragmentation. We tram fected 5AHSmyccells with mci-I and found that clones expressing the introduced Mel-i protein exhibited reduced DNA fragmentation. Mel-i was also capable of delaying the onset of cell death as judged by loss of membrane integrity, although it could not provide complete protection from c-Myc overexpression. Thus, Mel-i has functional homology to Bcl-2 in that Mel-i can enhance cell viability under conditions that otherwise cause apoptosis.