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Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755-3835
Mcl-1, a protein increased early in the differentiation of human myeloblastic ML-1 cells, has sequence similarity to Bcl-2. In the present study, we determined whether Mcl-1 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 apoptosis as determined by internucleosomal DNA fragmentation. We transfected 5AHSmyc cells with mcl-1 and found that clones expressing the introduced Mcl-1 protein exhibited reduced DNA fragmentation. Mcl-1 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, Mcl-1 has functional homology to Bcl-2 in that Mcl-1 can enhance cell viability under conditions that otherwise cause apoptosis.
1 This study was supported by NIH Grants CA50224 (A. E.) and CA57359 (R. W. C.), and Cancer Center Support Grant CA23108. J. E. R. was supported by National Cancer Institute Cancer Biology Training Grant CA09658.
2 To whom requests for reprints should be addressed.
Received 9/21/94. Accepted 11/ 2/94.
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