Identification of DDX1 as a JC Virus Transcriptional Control Region‐Binding Protein

Sunden, Yuji; Semba, Shingo; Suzuki, Tadaki; Okada, Yuki; Orba, Yasuko; Nagashima, Kazuo; Umemura, Takashi

doi:10.1111/j.1348-0421.2007.tb03915.x

Cited by 22 publications

(16 citation statements)

References 23 publications

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“…Roles proposed for DDX1 include RNA processing [26,34], transcription regulation [24], DNA double-strand break repair [29], and RNA transport [27,28]. While the first three roles are strictly dependent on the presence of DDX1 protein in the nucleus, RNA transport involves shuttling of molecules between the nucleus and cytoplasm, and to specific regions of the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

DEAD box 1: a novel and independent prognostic marker for early recurrence in breast cancer

Germain

Graham

Glubrecht

et al. 2010

Breast Cancer Res Treat

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Breast cancer is a heterogeneous disease characterized by diverse molecular signatures and a variable response to therapy. Clinical management of breast cancer is guided by the expression of estrogen and progesterone receptors and HER2 amplification. New prognostic and predictive markers, as well as additional targets for therapy, are needed for more effective management of this disease. Gene expression microarrays were probed with RNAs from 176 primary breast cancer samples and tissue microarrays immunostained with anti-DDX1 antibody, an antibody to DEAD box protein DDX1, a putative RNA-RNA and RNA-DNA unwinding protein normally found in the nucleus. Half of the patient cohort had experienced early relapse despite standard adjuvant therapy, but were otherwise matched for estrogen receptor and HER2 status, stage and duration of follow-up. Here, we identify DDX1 RNA overexpression as an independent prognostic marker for early recurrence in primary breast cancer, with a hazard ratio of 4.31 based on logrank analysis of Kaplan-Meier curves. Elevated levels of DDX1 protein in the cytoplasm also independently correlate with early recurrence with a hazard ratio of 1.90. In conclusion, our data indicate a strong and independent association between poor prognosis and deregulation of the DEAD box protein DDX1. We propose that elevated levels of DDX1 RNA or the presence of DDX1 in the cytoplasm could serve as an effective prognostic biomarker for early recurrence in primary breast cancer.

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Section: Discussionmentioning

confidence: 99%

DEAD box 1: a novel and independent prognostic marker for early recurrence in breast cancer

Germain

Graham

Glubrecht

et al. 2010

Breast Cancer Res Treat

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“…DDX1 is expressed at much higher levels in the JCV-susceptible cell line IMR-32 than in nonsusceptible cell lines. DDX1 significantly increased transactivation of the JCV promoter and enhanced the expression of JCV proteins in JCV-infected cells, while knockdown of DDX1 using small interfering RNA suppressed the expression of JCV proteins (113,114). The small JCV regulatory protein agnoprotein has also been shown to have a critical role in JCV regulation (55).…”

Section: Recent Studies Of Primate Polyomavirusesmentioning

confidence: 99%

“…Thus, downregulation of NF-1A expression in JCV-nonsusceptible cells, such as HeLa cells, resulted in a susceptibility for JCV multiplication. Recently, the DEAD box protein 1 (DDX1), an RNA helicase, and the cleavage stimulation factor (CstF) were shown to form a complex that binds to the JCV NCCR (113,114). DDX1 is expressed at much higher levels in the JCV-susceptible cell line IMR-32 than in nonsusceptible cell lines.…”

Section: Recent Studies Of Primate Polyomavirusesmentioning

confidence: 99%

Regulation of Gene Expression in Primate Polyomaviruses

White

Safak

Khalili

2009

J Virol

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Polyomaviruses are a growing family of small DNA viruses with a narrow tropism for both the host species and the cell type in which they productively replicate. Species host range may be constrained by requirements for precise molecular interactions between the viral T antigen, host replication proteins, including DNA polymerase, and the viral origin of replication, which are required for viral DNA replication. Cell type specificity involves, at least in part, transcription factors that are necessary for viral gene expression and restricted in their tissue distribution. In the case of the human polyomaviruses, BK virus (BKV) replication occurs in the tubular epithelial cells of the kidney, causing nephropathy in kidney allograft recipients, while JC virus (JCV) replication occurs in the glial cells of the central nervous system, where it causes progressive multifocal leukoencephalopathy. Three new human polyomaviruses have recently been discovered: MCV was found in Merkel cell carcinoma samples, while Karolinska Institute Virus and Washington University Virus were isolated from the respiratory tract. We discuss control mechanisms for gene expression in primate polyomaviruses, including simian vacuolating virus 40, BKV, and JCV. These mechanisms include not only modulation of promoter activities by transcription factor binding but also enhancer rearrangements, restriction of DNA methylation, alternate early mRNA splicing, cis-acting elements in the late mRNA leader sequence, and the production of viral microRNA.Polyomaviruses comprise a family of small nonenveloped DNA tumor viruses which have small, circular, doublestranded DNA genomes, have been isolated from many species of mammals and birds, and are characterized by a very limited host range with respect to the species that they can productively infect (48). We will focus mainly on three primate viruses, simian vacuolating virus 40 (SV40), BK virus (BKV), and JC virus (JCV), not only because they have taught us important lessons about eukaryotic molecular biology but also because BKV and JCV cause important human diseases. SV40 was discovered almost 50 years ago (115) and was the first primate polyomavirus to be described. SV40 differs significantly from the previously discovered mouse polyoma virus (111) in that it does not possess a middle T antigen in the early region and it expresses an accessory regulatory protein, agnoprotein, which is encoded in the late region. The species of origin of SV40 is the rhesus macaque, and the virus was discovered as a contaminant in early batches of polio vaccine. While the polio vaccinations at that time likely infected many people, the prevalence of SV40 infections in humans today has been debated (36,122). In 1971, two bona fide human polyomaviruses were discovered. BKV, also known as polyomavirus BK, was first isolated by Gardner et al. (37) by culture in Vero cells from the urine of a patient receiving immunosuppressive therapy following kidney transplantation. BKV is widespread throughout the human population around...

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“…59 The binding of DDX1 to Rev may target DDX1 to incompletely spliced transcripts. 60 DDX1 has also been associated with the lifecycle of polyoma and coronaviruses, 61,62 and of HCV. 63 Similar to DDX1, DDX3 enhances the Rev-dependent export of unspliced transcripts from the nucleus, 64 presumably by acting as a nucleo-cytoplasmatic shuttle protein.…”

mentioning

confidence: 99%