Disease relevance of DDX1

• Expression of two dead box genes (DDX1 and DDX6) is independent of that of MYCN in human neuroblastoma cell lines [1].
• Recently, we have shown that the novel DDX1 gene containing a DEAD box motif maps to the same chromosome band as MYCN at 2p24 and is co-amplified with MYCN in retinoblastoma cell lines [2].
• Therefore, alterations in DDX1-Rev interactions could induce HIV-1 persistence and targeting DDX1 may lead to rationally designed and novel anti-HIV-1 strategies and therapeutics [3].
• Reduced levels of DEAD-box proteins DBP-RB and p72 in fetal Down syndrome brains [4].

High impact information on DDX1

• DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp, are putative RNA helicases implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly [5].
• No evidence for correlation of DDX1 gene amplification with improved survival probability in patients with MYCN-amplified neuroblastomas [6].
• Coamplification of DDX1 correlates with an improved survival probability in children with MYCN-amplified human neuroblastoma [7].
• Coamplification is correlated to an upregulated gene expression for DDX1 and NAG [7].
• Although inhibitors of RNA transcription had no effect on DDX1 bodies or cleavage bodies, inhibitors of DNA replication resulted in loss of CstF-64-containing cleavage bodies [8].

Biological context of DDX1

• By microscopic fluorescence resonance energy transfer, we show that labeled DDX1 resides within a Förster distance of 10 nm of labeled CstF-64 protein in both the nucleoplasm and within cleavage bodies [9].
• We determined the gene copy number of DDX1 in 32 neuroblastoma patient samples (representative of all stages): 13 were MYCN amplified and 19 had normal copy numbers of the MYCN gene [2].
• All four nuclear bodies associate with each other during S phase, with cleavage bodies colocalizing with DDX1 bodies, and cleavage bodies/DDX1 bodies residing adjacent to gems and CBs [8].
• In addition to the eight conserved motifs that characterize all DEAD box proteins, the deduced amino acid sequence of DDX1 contains a subregion with considerable homology to heterogeneous nuclear ribonucleoprotein U [10].
• DEAD box proteins are putative RNA helicases that function in all aspects of RNA metabolism, including translation, ribosome biogenesis, and pre-mRNA splicing [9].

Anatomical context of DDX1

• DDX1, however was found to be amplified along with N-myc in 4/6 (67%) cell lines and 6/16 (38%) of the N-myc amplified tumours [11].
• We conclude that altered DDX1 expression in human astrocytes is, at least in part, responsible for the unfavorable cellular microenvironment for Rev function in these CNS-based cells [12].

Physical interactions of DDX1

• Coimmunoprecipitation analysis indicates that a proportion of CstF-64 protein resides in the same complex as DDX1 [9].

Other interactions of DDX1

• These observations indicate that there is at least 1 other gene co-amplified with MYCN in a proportion of cases and that those patients with DDX1 co-amplification tend to relapse more quickly [13].
• An RNA helicase, DDX1, interacting with poly(A) RNA and heterogeneous nuclear ribonucleoprotein K [14].
• Three identified proteins (PCBP2, G3BP1, and DDX1) were selected for further investigation into their possible roles on the HCV replication [15].

Analytical, diagnostic and therapeutic context of DDX1

• Immunofluorescence labeling of DDX1 demonstrated that in addition to widespread punctate nucleoplasmic labeling, DDX1 is found in discrete nuclear foci approximately 0.5 microm in diameter [9].
• Sequence analysis of the pG21 cDNA clone previously reported to represent an expressed gene frequently co-amplified with N-myc, showed this to be from the DDX1 gene [11].
• Based on YAC restriction mapping and content analysis, DDX1 maps 340 kb 5' of MYCN, outside the core domain of consistent amplification [16].
• We have determined the physical distance between the two genes by pulsed field gel electrophoresis in normal tissue and have found that DDX1 maps to a position at a maximum distance of 400 kbp 5' to MYCN [17].
• Quantification of MYCN, DDX1, and NAG gene copy number in neuroblastoma using a real-time quantitative PCR assay [18].

References