95 results about "Negative regulator" patented technology

The present invention provides methods for treating diseases or disorders, and methods for enhancing siRNA efficacy in RNAi, including administering to a subject or a biological system one or more siRNAs capable of down regulating the expression of one or more target genes and one or more siRNAs capable of down regulating the expression of one or more negative regulators of RNAi. The present invention also provides compositions including one or more siRNAs, or precursors thereof, capable of down regulating the expression of one or more target genes and comprising one or more siRNAs, or precursors thereof, capable of down regulating the expression of one or more negative regulators of RNAi.

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 provides a use of SIRT1 protein or agonists or up-regulators thereof for manufacturing a composition which can increase insulin sensitivity. SIRT1 can be used to increase insulin sensitivity by down-regulating expression of protein tyrosine phosphatase 1B, a negative regulator of insulin action.

The present invention feature antisense IAP oligonucleotides and other negative regulators of the IAP anti-apoptotic pathway, and methods for using them to enhance apoptosis.

Provided is a purified, negative regulator of osteoclast differentiation and bone resorption, specifically LRRc17. Further provided are methods and compositions for treating degenerative bone disorders, and treatments and prophylactic approaches for regulating bone resorption, and for decreasing or inhibiting the excessive bone loss associated with abnormal or excessive generation of or activity of osteoclasts.

The present invention relates to a TGF-β1 binding protein called r150. This protein has a GPI-anchor contained in r150 itself and not on a tightly associated protein and that it binds TGF-β1 with an affinity comparable to those of the signaling receptors. Furthermore, the released (soluble) form of this protein binds TGF-β1 independent of the types I and II receptors. Also, the soluble form inhibits the binding of TGF-β to its receptor. In addition, evidence that r150 is released from the cell surface by an endogenous phospholipase C is provided. Also, the creation of a mutant human keratinocyte cell line with a defect in GPI synthesis which displays reduced expression of r150 is described. Our results using these mutant keratinocytes suggest that the membrane anchored form of r150 is a negative modulator of TGF-beta responses. These findings, taken together with the observation that r150 forms a heteromeric complex with the signaling receptors, suggest that this accessory receptor in either its membrane anchored or soluble form may antagonize TGF-β responses in human keratinocytes. Experiments with mutants confirmed that TGFβ1 activity can be modulated when the expression of the accessory receptor r150 is silenced. The complete nucleic acid and deduced amino acid sequences are now provided. The r150 cloned nucleic acid was used to study overexpression of r150. When r150 gene is overexpressed, TGFβ responses are increased. r150 and its derivatives or precursors (fragments, variants and nucleic acids encoding the same) will find a broad clinical utility, knowing that TGFβ1 is an important cytokine.

The ability of miR-181a to support active signaling between Notch and pre-TCR pathways by coordinately dampening negative regulators of these pathways allows the use of miR-181a as a therapeutic target for T-ALL.

We identify markers capable of guiding the decision to incorporate epidermal growth factor receptor (EGFR) inhibitors, in particular EGFR tyrosine kinase inhibitors (TKIs), into chemotherapeutic regimens. Mitogen-inducible gene 6 (Mig6), a negative regulator of EGFR, is selectively upregulated during the development of resistance to the EGFR tyrosine kinase inhibitor (TKI) erlotinib, resulting in decreased EGFR phosphorylation. The ratio of Mig6 / EGFR expression highly correlates with erlotinib sensitivity. A low Mig6 / EGFR ratio correlates with a high response rate to gefitinib and a marked increase in progression-free survival for patients. The ratio of Mig6 to EGFR is a major predictor of biologic and clinical responses to EGFR inhibitors.

MicroRNAs (miRNAs) are a diverse and abundant class of ˜22-nucleotide (nt) endogenous regulatory RNAs that play a variety of roles in animal cells by controlling gene expression at the posttranscriptional level. Increased miR-181a expression in mature T cells is shown to cause a marked increase in T cell activation and augments T cell sensitivity to peptide antigens. Moreover, T cell blasts with higher miR-181a expression become reactive to antagonists. The effects of miR-181a on antigen discrimination are in part achieved by dampening the expression of multiple negative regulators in the T cell receptor (TCR) signaling pathway, including PTPN22 and the dual specificity phosphatases DUSP5 and DUSP6. This results in a reduction in the TCR signaling threshold, thus quantitatively and qualitatively enhancing T cell sensitivity to antigens.

Methods and compositions to suppress renin expression and blood pressure in mammals are disclosed. Vitamin D and its analogues and derivatives, including Gemini compounds, are negative regulators of renin synthesis and blood pressure. Renin expression and plasma angiotensin II production were increased several fold in vitamin D receptor (VDR) null mice, leading to hypertension, cardiac hypertrophy and increased water intake. Vitamin D or its analogue-mediated regulation of renin expression and blood pressure is independent of calcium metabolism. Vitamin D analogues or derivatives are novel preventive or therapeutic anti-hypertension agents. Assays to identify novel vitamin D analogues or derivatives as anti-hypertensive agents are disclosed.

The invention belongs to the technical field of plant genetic engineering and in particular relates to isolation cloning and functional verification of a DNA fragment which contains rice disease resistance related genes OsDR9. The resistance of rice to rice blast and brown spot disease is intensified through inhibiting expression of the OsDR9 genes in the rice, the OsDR9 genes are proved to be negative regulators in reaction that the rice resists fungous diseases, and disease-resistant rice varieties are cultured through inhibiting the expression of the OsDR9 genes.

The effect of EPO on the phosphorylation of the EPO receptor, the activation of the MAP Kinase pathway, and the expression of SHP-1 were analyzed. EPO was observed to cause a decrease in the expression of its negative regulator SHP-1. The decrease observed at both the mRNA and protein level was dose dependent and persisted as long as 24 hr following EPO treatment. EPO can down regulate the expression of its own negative regulator as a means for increased potency in neurons. Assays were generated to identify compounds that are useful in regulating SHP1 activity in neural cells.