An N-Myc truncation analogous to c-Myc-S induces cell proliferation independently of transactivation but dependent on Myc homology box II
An N-Myc truncation analogous to c-Myc-S induces cell proliferation independently of transactivation but dependent on Myc homology box II
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DOI：
10.1038/sj.onc.1210734
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发表时间：
2008-02-21
期刊：
影响因子：
8
通讯作者：
Cole, M. D.
中科院分区：
文献类型：
--
作者：
Cowling, V. H.;Cole, M. D.
Myc通过激活和抑制靶基因促进正常细胞增殖和致癌转化。c-Myc-S蛋白是c-Myc的截短形式，其在一些细胞中从内部AUG密码子处的翻译起始产生。我们报告说，c-Myc-S和类似的截短形式的N-MycWT可以完全挽救myc无效的成纤维细胞的增殖缺陷，但救援是依赖于高度保守的Myc同源盒II（MBII）。全球基因表达研究表明，N-Myc等效的c-Myc-S是有缺陷的几乎所有的Myc靶基因的转录激活，但仍然活跃的大部分转录抑制。Myc-S的抑制依赖于MBII，但它不与几种已知的核辅因子结合。这些数据表明，抑制Myc涉及招聘一种新的MBII依赖性辅因子。
Myc promotes both normal cell proliferation and oncogenic transformation through the activation and repression of target genes. The c-Myc-S protein is a truncated form of c-Myc that is produced in some cells from translation initiation at an internal AUG codon. We report that c-Myc-S and a similar truncated form of N-MycWT can fully rescue the proliferation defect in myc-null fibroblasts, but rescue is dependent on the highly conserved Myc homology box II (MBII). Global gene expression studies show that the N-Myc equivalent of c-Myc-S is defective for virtually all transcriptional activation of Myc target genes but remains active for the majority of transcriptional repression. Repression by Myc-S is dependent on MBII, but it does not bind to several known nuclear cofactors. These data suggest that repression by Myc involves recruitment of a novel MBII-dependent cofactor.