Cellular Genes (cellular + gene)

Distribution by Scientific Domains
Medical Sciences62%

Terms modified by Cellular Genes

  • cellular gene expression
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    Selected Abstracts

    Transcriptional activity of interferon regulatory factor (IRF)-3 depends on multiple protein,protein interactions

    FEBS JOURNAL, Issue 24 2002
    Hongmei Yang
    Virus infection results in the activation of a set of cellular genes involved in host antiviral defense. IRF-3 has been identified as a critical transcription factor in this process. The activation mechanism of IRF-3 is not fully elucidated, yet it involves a conformational change triggered by the virus-dependent phosphorylation of its C-terminus. This conformational change leads to nuclear accumulation, DNA binding and transcriptional transactivation. Here we show that two distinct sets of Ser/Thr residues of IRF-3, on phosphorylation, synergize functionally to achieve maximal activation. Remarkably, we find that activated IRF-3 lacks transcriptional activity, but activates transcription entirely through the recruitment of the p300/CBP coactivators. Moreover, we show that two separate domains of IRF-3 interact with several distinct regions of p300/CBP. Interference with any of these interactions leads to a complete loss of transcriptional activity, suggesting that a bivalent interaction is essential for coactivator recruitment by IRF-3. [source]

    Nuclear import and DNA-binding activity of RFX1

    FEBS JOURNAL, Issue 10 2001
    Evidence for an autoinhibitory mechanism
    RFX1 binds and regulates the enhancers of a number of viruses and cellular genes. RFX1 belongs to the evolutionarily conserved RFX protein family that shares a DNA-binding domain and a conserved C-terminal region. In RFX1 this conserved region mediates dimerization, and is followed by a unique C-terminal tail, containing a highly acidic stretch. In HL-60 cells nuclear translocation of RFX1 is regulated by protein kinase C with unknown mechanisms. By confocal fluorescence microscopy, we have identified a nonclassical nuclear localization signal (NLS) at the extreme C-terminus. The adjacent ,acidic region', which showed no independent NLS activity, potentiated the function of the NLS. Subcellular fractionation showed that the tight association of RFX1 with the nucleus is mediated by its DNA-binding domain and enhanced by the dimerization domain. In contrast, the acidic region inhibited nuclear association, by down-regulating the DNA-binding activity of RFX1. These data suggest an autoinhibitory interaction, which may regulate the function of RFX1 at the level of DNA binding. The C-terminal tail thus constitutes a composite localization domain, which on the one hand mediates nuclear import of RFX1, and on the other hand inhibits its association with the nucleus and binding to DNA. The participation of the acidic region in both activities suggests a mechanism by which the nuclear import and DNA-binding activity of RFX1 may be coordinately regulated by phosphorylation by kinases such as PKC. [source]

    A role for endogenous reverse transcriptase in tumorigenesis and as a target in differentiating cancer therapy

    GENES, CHROMOSOMES AND CANCER, Issue 1 2006
    Paola Sinibaldi-Vallebona
    An unexpected result emerging from completion of the genome sequencing project is that a large portion of mammalian genomes is constituted by retrotransposons. A large body of published data supports the conclusion that retrotransposons are biologically active elements and indicates that retrotransposition is an ongoing process in mammalian genomes. Retroelements can act as insertional mutagens altering the coding integrity of genes and, recently, have been found to also affect the expression of cellular genes at the epigenetic level: in this light, they are a potential threat in that these events can trigger the onset of several pathologies including cancer. Retroelement genes, and particularly the gene coding for reverse transcriptase (RT), are typically expressed at high levels in transformed cells and tumors. In recent work, we have found that drug-mediated inhibition of the endogenous RT activity, or silencing of expression of active retrotransposons of the LINE-1 family by RNA interference, down-regulate cell growth and induce the activation of differentiating functions in several cancer cell lines. Moreover, the inhibition of endogenous RT activity in vivo antagonizes the growth of human tumors in animal models. In this review, we discuss newly emerging concepts on the role of retrotransposons and suggest that an abnormally high level of the RT activity that they encode may contribute to the loss of control in the proliferation and differentiation programs typical of transformed cells. In this light, RT-coding elements may be regarded as promising targets in the development of novel, differentiation-inducing approaches to cancer therapy. © 2005 Wiley-Liss, Inc. [source]

    Radiation-induced gene expression profile of human cells deficient in 8-hydroxy-2,-deoxyguanine glycosylase

    INTERNATIONAL JOURNAL OF CANCER, Issue 3 2006
    M. Ahmad Chaudhry
    Abstract The human OGG1 gene encodes a DNA glycosylase that is involved in the base excision repair of 8-hydroxy-2,-deoxyguanine (8-OH-dG) from oxidatively damaged DNA. Cellular 8-OH-dG levels accumulate in the absence of this activity and could be deleterious for the cell. To assess the role of 8-oxoguanine glycosylase (OGG1) in the cellular defense mechanism in a specific DNA repair defect background, we set out to determine the expression pattern of base excision repair genes and other cellular genes not involved in the base excision pathway in OGG1-deficient human KG-1 cells after ionizing radiation exposure. KG-1 cells have lost OGG1 activity due to a homozygous mutation of Arg229Gln. Gene expression alterations were monitored at 4, 8, 12 and 24 hr in 2 Gy irradiated cells. Large-scale gene expression profiling was assessed with DNA microarray technology. Gene expression analysis identified a number of ionizing radiation-responsive genes, including several novel genes. There were 2 peaks of radiation-induced gene induction or repression: one at 8 hr and the other at 24 hr. Overall the number of downregulated genes was higher than the number of upregulated genes. The highest number of downregulated genes was at 8 hr postirradiation. Genes corresponding to cellular, physiologic, developmental and extracellular processes were identified. The highest number of radiation-induced genes belonged to the signal transduction category, followed by genes involved in transcription and response to stress. Microarray gene expression data were independently validated by relative quantitative RT-PCR. Surprisingly, none of the genes involved in the base excision repair of radiation-induced DNA damage showed altered expression. © 2005 Wiley-Liss, Inc. [source]

    Differentially expressed cellular genes following HBV: potential targets of anti-HBV drugs?

    JOURNAL OF VIRAL HEPATITIS, Issue 4 2005
    J. Yang
    Summary., The aim of the study was to screen for cellular genes that are differentially expressed following hepatitis B virus (HBV) infection, in an attempt to identify potential targets of anti-HBV drugs. An oligonucleotide microarray containing 231 virus-infection-associated genes was prepared. Differential gene expression in HepG2.2.15 cells compared to control with HepG2 cells was analysed by this in-house microarray. The change in gene expression in HepG2.2.15 cells treated by lamivudine on days 4 and 8 after exposure was also studied. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to comfirm the differentially expressed genes induced by HBV and lamivudine. There were 31 upregulated and four downregulated genes in HepG2.2.15 cells compared with the HepG2 control cells. Eleven genes were consistently altered by lamivudine at both time points. Of the 31 genes that were upregulated in HepG2.2.15 cells, there were seven genes which were downregulated by lamivudine. Of the four downregulated genes, there was one gene which was upregulated by lamivudine. Of the differentially expressed genes induced by HBV and lamivudine, the expression of five genes was confirmed by semi-quantitative RT-PCR. These results shed new light on the effects of HBV and lamivudine on cellular gene expression. Differentially expressed genes induced by HBV and lamivudine could potentially become new anti-HBV drug targets in novel therapies. [source]

    The Role of Angiogenic and Wound Repair Factors During CMV-Accelerated Transplant Vascular Sclerosis in Rat Cardiac Transplants

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2008
    D. N. Streblow
    Human cytomegalovirus (HCMV) accelerates transplant vascular sclerosis (TVS), a consequence of angiogenesis (AG) and wound repair (WR). While HCMV can be localized to TVS lesions, the low number of infected cells suggests a global effect on target tissues. We used microarray analysis followed by real-time-polymerase chain reaction (RT-PCR) in an RCMV-accelerated TVS rat cardiac transplant model to determine whether CMV activates host WR and AG factors. Dysregulated cellular genes in allografts from RCMV-infected recipients were compared to those from uninfected recipients and native hearts. We demonstrated that RCMV upregulates the genes involved in WR and AG, which was highest during the critical time of TVS acceleration (21,28 days). Using a standard in vitro AG assay, virus and serum-free supernatants collected at 48 h postinfection significantly induced endothelial cell (EC) migration, branching and tubule formation compared to supernatants from mock-infected cells. Supernatants from ultraviolet (UV)-inactivated RCMV-infected cells failed to induce AG, indicating that virus replication is required. Upregulation of WR and AG genes occurs during the critical period of CMV-accelerated TVS. Targeting these genes may prevent this process and improve allograft survival. [source]

    Pack-MULEs: theft on a massive scale

    BIOESSAYS, Issue 4 2005
    Damon Lisch
    It has been known for some time that plant transposons can capture and mobilize cellular genes. Recent work by Jiang and coworkers(1) has revealed that this process has happened on a massive scale. They found that portions of more than 1000 genes in rice have been captured and mobilized by members of the MULE family of transposons. In rice, and perhaps other plants as well, it appears that thousands of genes and portions of genes have been duplicated, transposed and rearranged. These results have fascinating implications for our understanding of the mode and tempo of gene evolution in plants. BioEssays 27:353,355, 2005. © 2005 Wiley periodicals, Inc. [source]