ONCOGENIC ACTIVITY OF THE C-MYC PROTEIN REQUIRES DIMERIZATION WITH MAX
ONCOGENIC ACTIVITY OF THE C-MYC PROTEIN REQUIRES DIMERIZATION WITH MAX
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DOI：
10.1016/0092-8674(93)90663-b
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发表时间：
1993-01-29
期刊：
影响因子：
64.5
通讯作者：
LAND, H
中科院分区：
文献类型：
--
作者：
AMATI, B;BROOKS, MW;LAND, H
c-Myc（Myc）和Max蛋白通过碱性-螺旋-环-螺旋-亮氨酸拉链基序（b-HLH-LZ）二聚化并结合DNA。使用遗传学方法，我们证明了与Max的结合对于Myc转化活性是必不可少的，并且Myc同源二聚体是无活性的。通过交换HLH-LZ结构域或间接修饰LZ二聚化特异性，产生相互有效结合但不与其野生型配偶体结合的Myc和Max突变体。虽然转化缺陷本身，互补突变体恢复Myc转化活性时，在细胞中共表达。HLH-LZ交换突变体对野生型Myc功能也具有显性负活性。此外，野生型max以剂量依赖性方式拮抗myc功能，推测是通过Max-Max和Myc-Max二聚体竞争共同的靶DNA位点。因此，Max可以作为Myc的抑制剂和激活剂发挥作用。讨论了Myc和Max在生长控制中的作用的一般模型。
c-Myc (Myc) and Max proteins dimerize and bind DNA through basic-helix-loop-helix-leucine zipper motifs (b-HLH-LZ). Using a genetic approach, we demonstrate that binding to Max is essential for Myc transforming activity and that Myc homodimers are inactive. Mutants of Myc and Max that bind efficiently to each other but not to their wild-type partners were generated by either exchanging the HLH-LZ domains or reciprocally modifying LZ dimerization specificities. While transformation defective on their own, complementary mutants restore Myc transforming activity when coexpressed in cells. The HLH-LZ exchange mutants also have dominant negative activity on wild-type Myc function. In addition, wild-type max antagonizes myc function in a dose-dependent manner, presumably through competition of Max-Max and Myc-Max dimers for common target DNA sites. Therefore, Max can function as both suppressor and activator of Myc. A general model for the role of Myc and Max in growth control is discussed.