致癌性的c-Myb N端缺失可调节DNA结合、反式激活以及与C/EBP的协同作用。

Tumorigenic N-terminal deletions of c-Myb modulate DNA binding, transactivation, and cooperativity with C/EBP.

作者信息

Oelgeschläger M, Kowenz-Leutz E, Schreek S, Leutz A, Lüscher B

机构信息

Institut für Molekularbiologie, Medizinische Hochschule Hannover, 30623 Hannover, Germany.

出版信息

Oncogene. 2001 Nov 1;20(50):7420-4. doi: 10.1038/sj.onc.1204922.

DOI:10.1038/sj.onc.1204922

PMID:11704872

Abstract

Oncogenic activation of c-myb by retroviral insertion has been implicated in tumor formation in chicken and mice. These genetic alterations result in deregulated expression of the c-myb gene and frequently in N-terminal truncation of the c-Myb protein. We demonstrate that truncation of the c-Myb N-terminus affects DNA binding and reporter activation. However, all three mutants, Myb Delta N20, Myb Delta N47 and Myb Delta N71 cooperated with C/EBP beta in reporter assays. In contrast to Myb Delta N20 and Myb Delta N47, however, the Myb Delta N71 mutant failed to activate the chromatin embedded endogenous mim-1 gene together with C/EBP beta. This suggests that an N-terminal region (amino acids 47-71) within repeat 1 (R1) of the murine c-Myb DNA binding domain affects activation of chromosomal target genes in collaboration with C/EBP beta.

摘要

逆转录病毒插入导致的c-myb致癌激活与鸡和小鼠的肿瘤形成有关。这些基因改变导致c-myb基因表达失调，并经常导致c-Myb蛋白的N端截短。我们证明，c-Myb N端的截短会影响DNA结合和报告基因激活。然而，在报告基因检测中，所有三个突变体Myb Delta N20、Myb Delta N47和Myb Delta N７1都与C/EBP β协同作用。然而，与Myb Delta N20和Myb Delta N47不同，Myb Delta N71突变体无法与C/EBP β一起激活染色质嵌入的内源性mim-1基因。这表明，小鼠c-Myb DNA结合结构域重复序列1（R1）内的N端区域（氨基酸47-71）与C/EBP β协同作用，影响染色体靶基因的激活。