Molecular Characterization of the DICE1 ( DDX26 ) Tumor Suppressor Gene in Lung Carcinoma Cells

We have determined the genomic structure of the candidate tumor suppressor gene DICE1 (DDX26). The DICE1 gene colocalizes with microsatellite 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.