1,721,067 research outputs found

    A new type of human interferon produced by peripheral blood mononuclear cells treated with inhibitors of transcription

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    Peripheral blood mononuclear cells from human normal donors treated with inhibitors of transcription produce a protein with the properties of interferon (IFN) [activity against a broad range of viruses, species specificity, lack of blockade of virus attachment, capability to induce in cells durable antiviral state, establishment of antiviral state requiring ongoing protein and RNA synthesis, capability to induce 2',5'-oligoadenylate synthetase]. This IFN-like protein has a molecular weight of approximately 7000 daltons and is not neutralized by antibody to alpha-, beta-, and gamma-IFNs tested singularly or in a pooled fashion. Taken together the data suggest that this IFN-like protein may indeed be a new type of human IFN

    Differential effects of gamma interferon on expression of HLA class II molecules controlled by the DR and DC loci.

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    Interferon-gamma affected the expression of the products of the immunoassociated antigen complex by a differential modulation of DR- and DC-locus-controlled molecules. In melanoma M14 cells treated with interferon-gamma, levels of DR molecules were increased two- to threefold, whereas levels of DC molecules were increased six- to sevenfold. Similar effects were induced on the two allelic products of each locus

    Disruption by SaCas9 endonuclease of HERV-Kenv, a retroviral gene with oncogenic and neuropathogenic potential, inhibits molecules involved in cancer and amyotrophic lateral sclerosis

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    The human endogenous retrovirus (HERV)-K, human mouse mammary tumor virus like-2 (HML-2) subgroup of HERVs is activated in several tumors and has been related to prostate cancer progression and motor neuron diseases. The cellular splicing factor 2/alternative splicing factor (SF2/ASF) is a positive regulator of gene expression, coded by a potent proto-oncogene, amplified, and abnormally expressed in tumors. TAR DNA-binding protein-43 (TDP-43) is a DNA/RNA-binding protein, negative regulator of alternative splicing, known for causing neurodegeneration, and with complex roles in oncogenesis. We used the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology, with the Cas9 system from Staphylococcus aureus (SaCas9), to disrupt the HERV-K(HML-2)env gene, and evaluated the effects on cultured cells. The tool was tested on human prostate cancer LNCaP cells, whose HERV-Kenv transcription profile is known. It caused HERV-K(HML-2)env disruption (the first reported of a HERV gene), as evaluated by DNA sequencing, and inhibition of env transcripts and proteins. The HERV-K(HML-2)env disruption was found to interfere with important regulators of cell expression and proliferation, involved in manaling, RNA-binding, and alternative splicing, such as epidermal growth factor receptor (EGF-R), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), SF2/ASF, and TDP-43. These novel findings suggest that HERV-K is not an innocent bystander, they reinforce its links to oncogenesis and motor neuron diseases, and they open potential innovative therapeutic options
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