Mcl-1, a member of the Bcl-2 family, delays apoptosis induced by c-Myc overexpression in Chinese hamster ovary cells.

Mcl-1, a member of the Bcl-2 family, delays apoptosis induced by c-Myc overexpression in Chinese hamster ovary cells.
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发表时间:
1994-12
期刊:
影响因子:
11.2
通讯作者:
J. Reynolds;Tao Yang;Liping Qian;J. Jenkinson;Ping Zhou;Alan Eastman;Roger Craig
J. Reynolds;Tao Yang;Liping Qian;J. Jenkinson;Ping Zhou;Alan Eastman;Roger Craig
中科院分区:
医学1区
文献类型:
--
作者:
J. Reynolds;Tao Yang;Liping Qian;J. Jenkinson;Ping Zhou;Alan Eastman;Roger Craig

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Mcl-1是在人成髓细胞ML-1分化早期增加的一种蛋白,其序列与Bcl-2相似。在本研究中,我们通过检测Mcl-1抑制c-Myc过表达诱导的细胞凋亡的能力来确定其是否与Bcl-2具有功能相似性。这是在热休克启动子的控制下,用含有人c-myc原癌基因的中国仓鼠卵巢5AHSmyc细胞进行的。热处理诱导c-Myc过表达,从而通过核小体间DNA片段确定细胞凋亡。我们用mcl-1转染5AHSmyc细胞,发现表达引入的mcl-1蛋白的克隆表现出较少的DNA片段化。Mcl-1也能够通过膜完整性的丧失来延缓细胞死亡的发生,尽管它不能对c-Myc过表达提供完全的保护。因此,Mcl-1在功能上与Bcl-2具有同源性,Mcl-1可以在导致细胞凋亡的条件下增强细胞活力。
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.