Reynolds J E, Yang T, Qian L, Jenkinson J D, Zhou P, Eastman A, Craig R W
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755-3835.
Cancer Res. 1994 Dec 15;54(24):6348-52.
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.
Mcl-1是一种在人髓母细胞ML-1细胞分化早期增加的蛋白质，其序列与Bcl-2相似。在本研究中，我们通过测试其抑制c-Myc过表达诱导的细胞凋亡的能力，来确定Mcl-1是否与Bcl-2具有功能相似性。这是利用中国仓鼠卵巢5AHSmyc细胞进行的，该细胞在热休克启动子的控制下含有人类c-myc原癌基因。热处理诱导c-Myc过表达，进而通过核小体间DNA片段化确定细胞凋亡。我们用mcl-1转染5AHSmyc细胞，发现表达导入的Mcl-1蛋白的克隆显示出DNA片段化减少。从细胞膜完整性丧失判断，Mcl-1也能够延迟细胞死亡的发生，尽管它不能完全保护细胞免受c-Myc过表达的影响。因此，Mcl-1与Bcl-2具有功能同源性，因为在其他情况下会导致细胞凋亡的条件下，Mcl-1可以增强细胞活力。
