Oncogenic point mutations in the Myb DNA-binding domain alter the DNA-binding properties of Myb at a physiological target gene
Oncogenic point mutations in the Myb DNA-binding domain alter the DNA-binding properties of Myb at a physiological target gene
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Myb DNA 结合域中的致癌点突变改变了 Myb 在生理靶基因上的 DNA 结合特性
DOI：
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发表时间：
2007
影响因子：
14.9
通讯作者：
K. Klempnauer
中科院分区：
文献类型：
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作者：
O. Ivanova;D. Braas;K. Klempnauer
禽成髓细胞病病毒（AMV）的癌蛋白v-Myb通过解除对特定靶基因的调控来转化髓细胞。先前的研究表明，v-Myb的致癌潜能通过截断c-Myb的N端和c端序列而被激活，并通过在dna结合域和蛋白质其他部分的氨基酸替换而进一步增加。我们分析了鸡溶菌酶基因的激活，该基因被c-Myb强烈激活，但不被其致癌对应物v-Myb激活。我们报道Myb作用于两个不同的顺式调控元件，位于基因上游的启动子和增强子。有趣的是，增强子的激活被致癌氨基酸取代所消除。我们证明了一个单独的Myb结合位点是Myb激活溶菌酶增强子的原因，并表明AMV的v-Myb蛋白不能与该位点结合。我们的数据首次证明了Myb的致癌激活改变了其在生理Myb靶基因上的dna结合特异性。
The oncoprotein v-Myb of avian myeloblastosis virus (AMV) transforms myelomonocytic cells by deregulating specific target genes. Previous work has shown that the oncogenic potential of v-Myb was activated by truncation of N- and C-terminal sequences of c-Myb and was further increased by amino acid substitutions in the DNA-binding domain and other parts of the protein. We have analyzed the activation of the chicken lysozyme gene which is strongly activated by c-Myb but not by its oncogenic counterpart v-Myb. We report that Myb acts on two different cis-regulatory elements, the promoter and an enhancer located upstream of the gene. Interestingly, the activation of the enhancer was abolished by the oncogenic amino acid substitutions. We demonstrated that a single Myb-binding site is responsible for the activation of the lysozyme enhancer by Myb and showed that the v-Myb protein of AMV was unable to bind to this site. Our data demonstrate for the first time that oncogenic activation of Myb alters its DNA-binding specificity at a physiological Myb target gene.
影响因子：
16
作者：
J. Leverson;Scott A. Ness
通讯作者：
J. Leverson;Scott A. Ness