Molecular characterization of the DICE1 (DDX26) tumor suppressor gene in lung carcinoma cells
Molecular characterization of the DICE1 (DDX26) tumor suppressor gene in lung carcinoma cells
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DOI：
10.3727/096504001108747503
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发表时间：
2001-01-01
影响因子：
3.1
通讯作者：
Wieacker, PF
中科院分区：
文献类型：
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作者：
Wieland, I;Röpke, A;Wieacker, PF
我们已经确定了候选抑癌基因DICE1（DDX26）的基因组结构。 DICE1 基因与微卫星标记 D13S284 端粒共定位于染色体区域 13q14.3 中的 RB1 基因。 DICE1 基因编码 18 个外显子，其前面是富含 GC 的启动子区域。发现预测 TATA 盒侧翼的 CpG 位点在肿瘤细胞中高度甲基化，并表现出 DICE1 表达降低。这表明 DICE1 基因可能发生肿瘤特异性转录沉默。在三种表达 DICE1 的细胞系中的两种中检测到异常剪接产物。预测的 DICE1 氨基酸序列在小鼠、果蝇 (D. melanogaster) 和线虫 (C. elegans) 中进化上是保守的。 ATP 依赖性解旋酶的死盒特征是 DICE1 及其小鼠和果蝇同源物中发现的主要基序。除 DEAD 盒之外的基序让人想起解旋酶超家族 II 的成员，但与典型的 DEAD 盒解旋酶有相当大的差异。 DICE1绿色荧光融合蛋白的表达表明DICE1优先定位于细胞核中。这表明 DICE1 参与 DNA 修复、转录或 RNA 剪接等核过程。
We have determined the genomic structure of the candidate tumor suppressor gene DICE1 (DDX26). The DICE1 gene colocalizes with rnicrosatellite marker D13S284 telomeric to the RB1 gene in chromosomal region 13q14.3. The DICE1 gene encodes 18 exons that are preceded by a GC-rich promoter region. CpG sites flanking a predicted TATA box were found to be hypermethylated in tumor cells that exhibited decreased DICE1 expression. This suggests tumor-specific transcriptional silencing of the DICE1 gene may occur. Aberrantly spliced products were detected in two of three DICE1-expressing cell lines, The predicted DICE1 amino acid sequence is evolutionarily conserved in mouse, fruit fly (D. melanogaster), and nematode (C. elegans). A DEAD box characteristic of ATP-dependent helicases is the predominant motif found in DICE1 and its mouse and fruit fly homologues. Motifs other than the DEAD box are reminiscent of members of the helicase superfamily II but there is considerable variation from the typical DEAD box helicases. Expression of DICE1 green fluorescent fusion protein showed a preferential localization of DICE1 in the nucleus. This suggests that DICE1 is involved in nuclear processes such as DNA repair, transcription, or RNA splicing.