TRANSCRIPTION ACTIVATION BY MYC AND MAX - FLANKING SEQUENCES TARGET ACTIVATION TO A SUBSET OF CACGTG MOTIFS IN-VIVO
TRANSCRIPTION ACTIVATION BY MYC AND MAX - FLANKING SEQUENCES TARGET ACTIVATION TO A SUBSET OF CACGTG MOTIFS IN-VIVO
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DOI：
10.1002/j.1460-2075.1993.tb06201.x
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发表时间：
1993-12-15
期刊：
影响因子：
11.4
通讯作者：
GODING, CR
中科院分区：
文献类型：
--
作者：
FISHER, F;CROUCH, DH;GODING, CR
Myc癌蛋白与细胞生长、分裂和分化的控制有关。虽然Myc含有一个bHLH-LZ基序，但它不能单独结合DNA，但可以通过与不相关的bHLH-LZ蛋白Max形成异二聚体来结合DNA。Max同二聚体和Myc-Max异二聚体共享结合CACGTG或CATGTG元件的能力。目前的模型，基于实验诱导的过表达的Myc和Max在哺乳动物细胞中，提出，Max-Max同源二聚体抑制，而Myc-Max异源二聚体通过CACGTG结合位点激活转录。使用哺乳动物细胞的结果的解释是复杂的存在许多不相关的CACGTG结合转录激活剂和存在两个替代的最大二聚化伙伴，Mad和Mxi-1。因此，Max过表达导致转录抑制的机制仍有待建立。使用酵母系统，我们表明，最大同源二聚体有可能通过CACGTG基序激活转录。Max的激活需要DNA结合和bHLH-LZ结构域外的氨基酸，但与Myc-Max异二聚体的激活相比减少。此外，Myc-Max异源二聚体而非Max-Max同源二聚体的转录激活在体内被核心CACGTG结合基序侧翼的特异性序列强烈抑制，推测反映了DNA结合亲和力降低。这些结果表明了一种机制，指导Myc-Max复合物的一个特定的子集CACGTG含有靶基因。
The Myc oncoprotein has been implicated in control of cell growth, division and differentiation. Although Myc contains a bHLH-LZ motif, it fails to bind DNA atone but can do so by forming heterodimers with an unrelated bHLH-LZ protein, Max. Max homodimers and Myc-Max heterodimers share the ability to bind CACGTG or CATGTG elements. Current models, based on experimentally induced overexpression of Myc and Max in mammalian cells, propose that Max-Max homodimers repress while Myc-Max heterodimers activate transcription through CACGTG binding sites. The interpretation of the results using mammalian celts is complicated by the presence of numerous unrelated CACGTG binding transcription activators and the existence of two alternative Max dimerization partners, Mad and Mxi-1. Thus, the mechanism whereby overexpression of Max leads to transcriptional repression remains to be established. Using a yeast system we show that Max homodimers have the potential to activate transcription through CACGTG motifs. Activation by Max requires DNA binding and amino acids outside the bHLH-LZ domain but is reduced compared with activation by Myc-Max heterodimers. Moreover, transcriptional activation by Myc-Max heterodimers, but not Max-Max homodimers, is strongly inhibited in vivo by specific sequences flanking the core CACGTG binding motif, presumably reflecting reduced DNA binding affinity. These results suggest a mechanism for directing the Myc-Max complex to a specific subset of CACGTG-containing target genes.