THE C-MYC PROTEIN INDUCES CELL-CYCLE PROGRESSION AND APOPTOSIS THROUGH DIMERIZATION WITH MAX
THE C-MYC PROTEIN INDUCES CELL-CYCLE PROGRESSION AND APOPTOSIS THROUGH DIMERIZATION WITH MAX
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DOI：
10.1002/j.1460-2075.1993.tb06202.x
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发表时间：
1993-12-15
期刊：
影响因子：
11.4
通讯作者：
LAND, H
中科院分区：
文献类型：
--
作者：
AMATI, B;LITTLEWOOD, TD;LAND, H
C-Myc蛋白(Myc)参与细胞转化和有丝分裂，但也是细胞程序性死亡或凋亡的有力诱导者。目前尚不清楚这些明显相反的功能是通过共同的还是不同的分子机制来调节的。MYC及其伴侣蛋白Max在体内外通过基本/螺旋-环-螺旋/亮氨酸拉链基序(bHLH-LZ)与DNA二聚化和结合。通过使用互补的亮氨酸拉链突变体(称为MycEG和MaxEG)，它们彼此之间有效地二聚体，而不是与它们的野生型伴侣，我们证明了Myc-Max二聚体诱导未转化的啮齿动物成纤维细胞的细胞周期进展和凋亡。单独的MycEG或MaxEG是不活跃的，但共表达恢复了阻止退出细胞周期并在去除生长因子时诱导细胞死亡的能力。因此，Myc可以通过与单个伴侣Max的二聚化来控制两种不同的细胞命运。
The c-Myc protein (Myc) is involved in cellular transformation and mitogenesis, but is also a potent inducer of programmed cell death, or apoptosis. Whether these apparently opposite functions are mediated through common or distinct molecular mechanisms remains unclear. Myc and its partner protein, Max, dimerize and bind DNA in vitro and in vivo through basic/helix-loop-helix/leucine zipper motifs (bHLH-LZ). By using complementary leucine zipper mutants (termed MycEG and MaxEG), which dimerize efficiently with each other but not with their wild-type partners, we demonstrate that both cell cycle progression and apoptosis in nontransformed rodent fibroblasts are induced by Myc-Max dimers. MycEG or MaxEG alone are inactive, but co-expression restores ability to prevent withdrawal from the cell cycle and to induce cell death upon removal of growth factors. Thus, Myc can control two alternative cell fates through dimerization with a single partner, Max.