Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Ku (p70/p80) autoantigen, a heterodimer consisting of 70 kDa (p70) and 80 kDa (p80) protein subunits, is one of a group of DNA-associated autoantigens identified as targets of autoantibodies produced by patients with SLE and related disorders. Many of these DNA-protein antigens are involved in organizing the genome into transcriptionally active (euchromatin) and inactive (heterochromatin) domains. The bulk of available evidence indicates that the Ku antigen is also involved in organizing the genome, although its precise role remains unclear. Molecular cloning of the protein subunits of Ku has revealed that the structure of p70 resembles that of certain transcriptional activator proteins, and there is some evidence in vitro that Ku may increase transcriptional activity from at least two promoters. Moreover, examination of the distribution of Ku in the polytene chromosomes of insects suggests an association with transcriptionally active chromatin. The DNA-binding domain of Ku has been localized to the C-terminus of p70, whereas p80 does not appear to bind DNA, and may be involved in interactions with other proteins. Epitope mapping and mutagenesis experiments have shown that the immunodominant epitope of p70 lies within the DNA-binding domain. Surprisingly, this autoepitope is not conserved between humans and mice, raising the possibility that the interaction of Ku with DNA might exhibit species specific functional differences. At least seven additional autoepitopes have been identified on the Ku particle, located on p70, p80, or both subunits. Autoantibodies to p70, p80, and DNA are produced tandemly by patients with SLE, providing evidence for an antigen-driven immune response targeting the entire Ku particle. The multiple specificities of anti-Ku autoantibodies and the tandem production of antibodies to the various constituents of the Ku particle are consistent with a role of either "molecular mimicry" or "intermolecular help" in the generation of autoimmunity to this antigen.
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PMID:Antibodies to the p70/p80 (Ku) antigens in systemic lupus erythematosus. 162 75

IL-2 gene expression in activated T-cells is initiated by chromatin remodeling at the IL-2 proximal promoter and conversion of a transcriptional repressor into a potent transcriptional activator. A purine-box regulator complex was purified from activated Jurkat T-cell nuclei based on sequence-specific DNA binding to the antigen receptor response element (ARRE)/nuclear factor of activated T-cells (NF-AT) target DNA sequence in the proximal IL-2 promoter. ARRE DNA-binding subunits were identified as NF90, NF45 and systemic lupus erythematosis autoantigens, Ku80 and Ku70. Monoclonal antibodies to Ku80, Ku70 and NF90 specifically inhibit constitutive and inducible ARRE DNA-binding activity in Jurkat T-cells. Ku80, Ku70 and NF90 bind specifically to the IL-2 gene promoter in vivo, as demonstrated by chromatin immunoprecipitation. Activation of Jurkat T-cells and mouse primary spleen cells induces binding of Ku80 and NF90 to the IL-2 promoter in vivo, and decreases binding of Ku70 to the IL-2 promoter in vivo, and these dynamic changes are inhibited by immunosuppressants cyclosporin A and triptolide. Dynamic changes in binding of Ku80, Ku70 and NF90 to the IL-2 proximal promoter in vivo correlate with chromatin remodeling and transcriptional initiation in activated T-cells.
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PMID:Dynamic binding of Ku80, Ku70 and NF90 to the IL-2 promoter in vivo in activated T-cells. 1738 50

Penicillium decumbens is an important industrial filamentous fungus and has been widely used in biorefinery due to its high production of cellulase and hemicellulase. However, molecular engineering has still rarely been applied for strain improvement in P. decumbens. It has been proven that gene targeting manipulation in many filamentous fungi is hampered by nonhomologous end-joining (NHEJ) pathway. To improve gene targeting efficiency in P. decumbens, the putative pku70 encoding the Ku70 homologue involved in the NHEJ pathway was identified and deleted. The Deltapku70 strain showed no apparent defect in vegetative growth, conidiation, and cellulase production, and displayed similar sensitivity to chemical agents of hygromycin B, ethyl methane sulfonate, and H2O2 at different concentrations compared with the wild-type strain. The effect of the absence of pku70 on gene targeting was tested by disruption of creA encoding a putative carbon catabolite repressor and xlnR encoding a putative transcriptional activator. Efficiency of gene targeting for both genes was 100% in the Deltapku70 strain, compared with the low efficiency in the wild-type recipient. Furthermore, the integration types for three single targeting cassettes and the cotransformation of two independent targeting cassettes were primarily investigated in P. decumbens. The highly efficient gene targeting system established in this study will open the way to large-scale functional genomic analysis in P. decumbens and contribute to the study of the mechanism of lignocellulose degradation by P. decumbens.
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PMID:Development of a highly efficient gene targeting system allowing rapid genetic manipulations in Penicillium decumbens. 2039 3