MCL-1, A MEMBER OF THE BCL-2 FAMILY, DELAYS APOPTOSIS INDUCED BY C-MYC OVEREXPRESSION IN CHINESE-HAMSTER OVARY CELLS

Mcl-1, a protein increased early in the differentiation of human myelo blastic ML-1 cells, has sequence similarity to Bcl-2. In the present s tudy, we determined whether Mcl-1 has functional similarity to Bcl-2 b y testing its ability to inhibit apoptosis induced by c-Myc overexpres sion. This was carried out using Chinese hamster ovary 5AHSmyc cells w hich contain the human c-myc proto-oncogene under the control of a hea t shock promoter. Heat treatment induces c-Myc overexpression and thus apoptosis as determined by internucleosomal DNA fragmentation. We tra nsfected 5AHSmyc cells with mcl-1 and found that clones expressing the introduced Mcl-1 protein exhibited reduced DNA fragmentation, Mcl-1 w as also capable of delaying the onset of cell death as judged by loss of membrane integrity, although it could not provide complete protecti on from c-Myc overexpression. Thus, Mcl-1 has functional homology to B cl-2 in that Mcl-1 can enhance cell viability under conditions that ot herwise cause apoptosis.