118 results about "Transactivation" patented technology

The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.

The present disclosure relates generally to novel methods and compositions for using engineered reprogramming factor(s) for the creation of induced pluripotent stem cells (iPSCs) through a kinetically controlled process. Specifically, this disclosure relates to establishing combinations of reprogramming factors, including fusions between conventional reprogramming factors with transactivation domains, optimized for reprogramming various types of cells. More specifically, the exemplary methods disclosed herein can be used for creating induced pluripotent stem cells from various mammalian cell types, including human fibroblasts. Exemplary methods of feeder-free derivation of human induced pluripotent stem cells using synthetic messenger RNA are also disclosed.

This application describes the cloning of p63, a gene at chromosome 3q27-29, that bears homology to the tumor suppressor p53. The p63 gene encodes at least six different isotypes. p63 was detected in a variety of human and mouse tissue and demonstrates remarkably divergent activities, such as the ability to transactivate p53 reporter genes and induce apoptosis. Isotopes of p63 lacking a transactivation domain act as dominant negatives towards the transactivation by p53 and p63.

The invention provides for the use of oligodeoxynucleotide decoys for the prophylactic or therapeutic treatment of diseases associated with the binding of endogenous transcription factors to genes involved in cell growth, differentiation and signalling or to viral genes. By inhibiting endogenous trans-activating factors from binding transcription regulatory regions, the decoys modulate gene expression and thereby regulating pathological processes including inflammation, intimal hyperplasia, angiogenesis, neoplasia, immune responses and viral infection. The decoys are administered in amounts and under conditions whereby binding of the endogenous transcription factor to the endogenous gene is effectively competitively inhibited without significant host toxicity. The subject compositions comprise the decoy molecules in a context which provides for pharmacokinetics sufficient for effective therapeutic use.

This invention provides a novel pyrin-only protein (POP2), polypeptides, nucleic acids encoding them and methods for making and using them. The polypeptides of this invention have nuclear factor-κB (NF-κB) modulating activity. NF-κB is pivotal for transactivation of cell-cycle regulatory, cytokine and adhesion molecule genes and is dysregulated in many cancers, neurodegenerative disorders, and inflammatory diseases. Proteins with Pyrin and / or caspase recruitment (CARD) domains have roles in apoptosis, innate immunity, and inflammation. Many pyrin domain proteins modulate NF-KB activity as well as participate in assembling both the perinuclear “apoptotic speck” and the pro-IL1β / IL-18 converting inflammasome complex. ‘Pyrin-only’ proteins are attractive as negative regulators of pyrin domain-mediated functions and one such protein, POP1, has been reported. We teach a second Pyrin-only protein (POP2). POP2 is a 294 nt single exon gene located on human chromosome 3 encoding a 97 amino acid protein with sequence and predicted structural similarity to other pyrin domains. Highly similar to pyrin domains in CATERPILLER (CLR, NLR, NALP) family proteins, POP2 is less like the prototypic Pyrin and ASC pyrin domains. POP2 is expressed principally in peripheral blood leukocytes and displays both cytoplasmic and nuclear expression patterns in transfected cells. TNFα-stimulated and p65 (RelA) induced NF-KB-dependent gene transcription is inhibited by POP2 in vitro by a mechanism involving changes in NF-κB nuclear import or distribution. While colocalizing with ASC in perinuclear specks, POP2 also inhibits the formation of specks by the CLR protein CIAS1 / NALP3. Together these observations indicate that POP2 is a negative regulator of NF-KB activity that may influence the assembly of pyrin-domain dependent complexes.

The present invention relates to methods to use non-steroidal ligands in nuclear receptor-based inducible gene expression system to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.

The present technology relates to a method of treating cancer by sensitizing human tumours to DNA damaging therapies through activating FBXO32 expression. Transactivation of FBXO32 through the inhibition of EZH2, a histone methyltransferase, decreases p21 protein induction which results in the sensitization of human tumours to chemotherapy. The method further provides a prognostic method to determine if a combination treatment would be effective.

The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.

The present invention is directed to a method for screening and identifying molecules that transactivate a neurotrophin receptor and mediate neuronal cell survival in the absence of neurotrophins which uses one or a combination of three different assays. The assays involve detecting the phosphorylation of a neurotrophin receptor, detecting the phosphorylation of phosphotidylinositol 3′-kinase or Akt enzyme, and assessing neuronal cell survival in the absence of neurotrophins.

Methods for altering levels in plants of one or more phenolic compounds that are intermediates or final products of the plant phenylpropanoid pathway are provided. One method comprises transforming a plant cell with an expression construct comprising a nucleic acid which encodes a transactivator protein comprising the myb domain of the maize “ZmMyb-IF35” protein and an activation domain. Another method comprises transforming a plant cell with an expression construct comprising a transgene which encodes an antisense ZmMyb-IF35 RNA. The present invention also relates to expression constructs and vectors used in the present methods, transformed plant cells and transgenic plants prepared according to the present methods, and the seeds of such transgenic plants.

The presently claimed invention offers programmable and precise regulation of Cas9 functions by utilizing a set of compact Cas9 derivatives created by deleting conserved HNH and / or REC-C domains based on the structural information across variant class 2 CRISPR effectors. In addition, a novel strategy for engineering the dimeric gRNA-guided nuclease by splitting the mini-dSaCas9 and fusing the FokI domain right after the split point is claimed to increase the on-target DNA cleavage efficiency and potentially reduce the off-target effect because of a closer proximity of dimeric FokI nuclease to the target sequence. By combining the optimized and compact gRNA expression cassette and the downsized SaCas9 derivatives, the entire CRISPR / Cas system with different effector domains for transactivation, DNA cleavage and base editing is loaded into a single AAV virus. Such an all-in-one AAV-CRISPR / Cas9 system will be particularly appealing in biomedical applications that require safe and efficient delivery in vivo.

The present invention provides a method for screening for progesterone receptor isoform specific ligands as well as a first method for screening for tissue-selective progesterone receptor ligands, both methods comprising selecting progesterone receptor isoform A or progesterone receptor isoform B selective ligands by means of an assay involving cells stably transfected with plasmids expressing the progesterone receptor isoform A or B. Furthermore, the present invention provides a second method for screening for tissue-selective progesterone receptor ligands, comprising in vivo tests in desired target tissues. The present invention further relates to cell lines suitable for this transactivation assay, a respective assay kit and medical uses of the isoform-specific and / or tissue-selective progesterone receptor ligands according to the present invention.

This invention relates to a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene. The ligands comprise a class of ketones.