MAX - A HELIX-LOOP-HELIX ZIPPER PROTEIN THAT FORMS A SEQUENCE-SPECIFIC DNA-BINDING COMPLEX WITH MYC
MAX - A HELIX-LOOP-HELIX ZIPPER PROTEIN THAT FORMS A SEQUENCE-SPECIFIC DNA-BINDING COMPLEX WITH MYC
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DOI：
10.1126/science.2006410
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发表时间：
1991-03-08
期刊：
影响因子：
56.9
通讯作者：
EISENMAN, RN
中科院分区：
文献类型：
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作者：
BLACKWOOD, EM;EISENMAN, RN
myc原癌基因家族与细胞增殖、分化和肿瘤形成有关，但其在分子水平上的功能机制尚不清楚。Myc家族蛋白的羧基端含有一个基本区域螺旋-环-螺旋亮氨酸拉链基序（bHLH-Zip），该基序具有dna结合活性，并被预测介导蛋白-蛋白相互作用。利用c-Myc的bHLH-Zip区筛选互补DNA （cDNA）表达文库，鉴定出bHLH-Zip蛋白，命名为Max。Max特异性与c-Myc、N-Myc和L-Myc蛋白相关，但与其他一些bHLH、bZip或bHLH- zip蛋白无关。Max与c-Myc之间的相互作用依赖于c-Myc HLH-Zip结构域的完整性，而不依赖于基本区或结构域外的其他序列。此外，在Max和Myc都没有明显结合的情况下，Myc-Max复合物以序列特异性的方式与DNA结合。该复合物的dna结合活性依赖于二聚化结构域和c-Myc的基本区。这些结果表明，Myc家族蛋白在细胞中进行一组有限的相互作用，可能属于真核生物dna结合转录因子的更一般的类别。
The myc protooncogene family has been implicated in cell proliferation, differentiation, and neoplasia, but its mechanism of function at the molecular level is unknown. The carboxyl terminus of Myc family proteins contains a basic region helix-loop-helix leucine zipper motif (bHLH-Zip), which has DNA-binding activity and has been predicted to mediate protein-protein interactions. The bHLH-Zip region of c-Myc was used to screen a complementary DNA (cDNA) expression library, and a bHLH-Zip protein, termed Max, was identified. Max specifically associated with c-Myc, N-Myc, and L-Myc proteins, but not with a number of other bHLH, bZip, or bHLH-Zip proteins. The interaction between Max and c-Myc was dependent on the integrity of the c-Myc HLH-Zip domain, but not on the basic region or other sequences outside the domain. Furthermore, the Myc-Max complex bound to DNA in a sequence-specific manner under conditions where neither Max nor Myc exhibited appreciable binding. The DNA-binding activity of the complex was dependent on both the dimerization domain and the basic region of c-Myc. These results suggest that Myc family proteins undergo a restricted set of interactions in the cell and may belong to the more general class of eukaryotic DNA-binding transcription factors.