Valentijn Linda J, Koster Jan, Versteeg Rogier
Department of Human Genetics, M1-134, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
Genomics. 2006 Apr;87(4):483-9. doi: 10.1016/j.ygeno.2005.11.004. Epub 2006 Jan 25.
NM23-H1 and NM23-H2 are neighboring genes on chromosome 17q. They encode nucleoside diphosphate kinases that have additional roles in signal transduction, transcription, and apoptosis. NM23-H1 expression is a strong marker for prognosis and metastatic behavior in many tumor types. A new bioinformatic tool, TranscriptView, identified read-through transcripts that start in the NM23-H1 gene and continue in the neighboring NM23-H2 gene. Splicing results in a transcript containing exons 1 to 4 of NM23-H1 and exons 2 to 5 of NM23-H2. The resulting mRNA encodes a novel and long variant of the NM23 protein family, NM23-LV, which contains part of NM23-H1 and the complete NM23-H2 protein. The transcript was amplified and sequenced from two neuroblastoma cell lines, confirming the presence of the predicted NM23-LV mRNA in vivo. Tissue analysis showed that NM23-LV is ubiquitously expressed, with the exception of the kidney. Neuroblastoma tumors show high-level expression of NM23-H1 and-H2 as well as NM23-LV mRNA. In neuroblastoma cells, the NM23-LV protein has mainly a cytoplasmic localization, but some nuclear staining was observed as well.
NM23-H1和NM23-H2是位于17号染色体q臂上的相邻基因。它们编码核苷二磷酸激酶,这些激酶在信号转导、转录和细胞凋亡中还具有其他作用。在许多肿瘤类型中,NM23-H1的表达是预后和转移行为的一个重要标志物。一种新的生物信息学工具TranscriptView识别出了起始于NM23-H1基因并延续至相邻的NM23-H2基因的通读转录本。剪接产生了一个包含NM23-H1的外显子1至4和NM23-H2的外显子2至5的转录本。所产生的mRNA编码NM23蛋白家族的一种新的长变体NM23-LV,它包含部分NM23-H1和完整的NM23-H2蛋白。该转录本从两个神经母细胞瘤细胞系中进行了扩增和测序,证实了体内存在预测的NM23-LV mRNA。组织分析表明,除肾脏外,NM23-LV在各处均有表达。神经母细胞瘤肿瘤显示出NM23-H1、-H2以及NM23-LV mRNA的高水平表达。在神经母细胞瘤细胞中,NM23-LV蛋白主要定位于细胞质,但也观察到了一些细胞核染色。