Wenzel A, Schwab M
Department of Cytogenetics, German Cancer Research Center, Heidelberg, Germany.
Eur J Cancer. 1995;31A(4):516-9. doi: 10.1016/0959-8049(95)00060-v.
The oncogenic activation by amplification of the MYCN gene is frequently observed in human neuroblastomas and occasionally in other tumours with neuronal qualities. As a consequence of amplification, elevated levels of the mycN protein are expressed. mycN contains a C-terminal basic region (BR) that can bind to DNA, and a helix-loop-helix (HLH)-leucine zipper (Zip) domain, which is responsible for the physical interaction with another HLH-Zip protein, max. This principle structure is conserved among all members of the MYC gene family. The resulting dimers can bind to the DNA sequence CACGTG. The mycN protein, but not max, contains, near the N-terminus, a region conferring the ability to activate the transcription of genes. mycN/max heterodimers probably activate and max/max homodimers repress transcription of, as yet, unidentified target genes. In neuroblastoma cells, where mycN is deregulated, the balanced interaction of BR-HLH-Zip proteins is probably perturbed, and, therefore, genes controlled by mycN might be abnormally expressed and thereby alter normal cell growth with the consequence of tumorigenesis.
MYCN基因扩增导致的致癌激活在人类神经母细胞瘤中经常可见，偶尔也见于其他具有神经元特征的肿瘤。作为扩增的结果，mycN蛋白表达水平升高。mycN包含一个可与DNA结合的C端碱性区域（BR），以及一个螺旋-环-螺旋（HLH）-亮氨酸拉链（Zip）结构域，该结构域负责与另一个HLH-Zip蛋白max进行物理相互作用。这种基本结构在MYC基因家族的所有成员中都是保守的。形成的二聚体可与DNA序列CACGTG结合。mycN蛋白在N端附近含有一个赋予激活基因转录能力的区域，而max则没有。mycN/max异二聚体可能激活，而max/max同二聚体可能抑制尚未确定的靶基因的转录。在mycN失调的神经母细胞瘤细胞中，BR-HLH-Zip蛋白的平衡相互作用可能受到干扰，因此，受mycN控制的基因可能会异常表达，从而改变正常细胞生长，导致肿瘤发生。
