MYC AND MAX PROTEINS POSSESS DISTINCT TRANSCRIPTIONAL ACTIVITIES
MYC AND MAX PROTEINS POSSESS DISTINCT TRANSCRIPTIONAL ACTIVITIES
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DOI：
10.1038/359426a0
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发表时间：
1992-10-01
期刊：
影响因子：
64.8
通讯作者：
EISENMAN, RN
中科院分区：
文献类型：
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作者：
KRETZNER, L;BLACKWOOD, EM;EISENMAN, RN
MyC家族蛋白被认为参与转录1，2，因为它们具有一个羧基末端碱性螺旋环螺旋拉链（bHLH-Z）结构域，这是一大类转录因子所共有的，以及一个氨基末端片段，当在嵌合体构建体中测定时，该片段对c-Myc具有反式激活功能4。此外，c-、N-和L-Myc蛋白在体外和体内与bHLH-Z蛋白Max 5 -8异二聚化。在体外，Max同二聚化，但优先与同二聚化较差的Myc缔合5，6。此外，Myc-Max异二聚体以比单独的同二聚体更高的亲和力特异性结合核苷酸序列CACGTG 9 5。Max的鉴定以及Myc和Max的特异性DNA结合活性为直接测试这些蛋白在哺乳动物细胞中的转录活性提供了机会。我们在这里报告，Myc过表达激活，而最大的过表达抑制，报告基因的转录。Max诱导的抑制通过c-Myc的过表达而缓解。抑制需要Max的DNA结合结构域，而抑制的缓解需要Myc的二聚化和转录激活活性。这两种效应都需要报告基因中的Myc-Max结合位点。
THE MyC family proteins are thought to be involved in transcription1,2 because they have both a carboxy-terminal basic-helix-loop-helix-zipper (bHLH-Z) domain, common to a large class of transcription factors, and an amino-terminal fragment which, for c-Myc, has transactivating function when assayed in chimaeric constructs4. In addition, c-, N- and L-Myc proteins heterodimerize, in vitro and in vivo, with the bHLH-Z protein Max5-8. In vitro, Max homodimerizes but preferentially associates with Myc, which homodimerizes poorly5,6. Furthermore Myc-Max heterodimers specifically bind the nucleotide sequence CACGTG9 with higher affinity than either homodimer alone5. The identification of Max and the specific DNA-binding activities of Myc and Max provides an opportunity for directly testing the transcriptional activities of these proteins in mammalian cells. We report here that Myc overexpression activates, whereas Max overexpression represses, transcription of a reporter gene. Max-induced repression is relieved by overexpression of c-Myc. Repression requires the DNA-binding domain of Max, whereas relief of repression requires the dimerization and transcriptional activation activities of Myc. Both effects require Myc-Max-binding sites in the reporter gene.