• STAT3
  • Subsequently, the phosphorylated STAT3 (pSTAT3) molecules form homodimers, which migrate to the nuclei where they bind to the promoters of various target genes and regulate their transcriptions [ 1 , 2 ]. (mdpi.com)
  • Many STAT3 targets, such as Survivin, Cyclins and the Bcl-2 family proteins, are known to promote cell proliferation and survival [ 1 , 3 , 4 ]. (mdpi.com)
  • STAT proteins, especially STAT3, are not only important in the development and function of normal cells, but can assume oncogenic properties when the extent and duration of their activation are disturbed ( 2 ). (aacrjournals.org)
  • STAT3 is constitutively phosphorylated and thereby activated in many forms of cancer. (aacrjournals.org)
  • Inhibition
  • Inhibition of SIRT1 by use of SIRT1 siRNA or SIRT1 inhibitors (amurensin G and EX527) effectively potentiated sensitivity of Hsp90 inhibitors (17-AAG and AUY922) in CD44 high K562 stem-like cells expressing high levels of CSC-related molecules including Oct4, CD34, β-catenin, c-Myc, mutant p53 (mut p53), BCRP and P-glycoprotein (P-gp) as well as CD44. (ijbs.com)
  • However, direct inhibition of Hsp90 leads to disruption of complexes of Hsp90 with heat shock factor 1 (HSF1), thereby causing HSF1-mediated induction of cytoprotective heat shock proteins (Hsps) such as Hsp70 and Hsp27, which contribute to resistance to Hsp90 inhibitors [ 10 ]. (ijbs.com)
  • The cellular response in signal transduction cascades involves alteration of the expression of effector genes or activation/inhibition of targeted proteins. (wikipedia.org)
  • Stat1
  • STAT1 has a key role in many gene expressions that cause survival of the cell, viability or pathogen response. (wikipedia.org)
  • 2 related patients had a homozygous missense STAT1 mutation which caused impaired splicing, therefore a defect in mature protein. (wikipedia.org)
  • Regulation
  • SIRT1 depletion caused significant down-regulation of heat shock factor 1 (HSF1)/heat shock proteins (Hsps) as well as these CSC-related molecules, which led to the sensitization of CD44 high K562 cells to Hsp90 inhibitor by SIRT1 inhibitor. (ijbs.com)
  • The pathway maps illustrate protein interactions and regulation to provide a comprehensive picture of signaling and disease processes. (bio-rad.com)
  • mutations
  • Activating mutations in FLT3 have been identified in approximately 30% of patients with acute myelogenous leukemia, making it one of the most common mutations observed in this disease. (jove.com)
  • Activated inflammatory cells release free radicals, such as reactive oxygen species (ROS) and nitric oxide (NO) reactive species, which in turn can cause DNA damage and lead to gene mutations, thus fostering neoplastic transformation. (hindawi.com)
  • RS is caused by loss-of-function mutations in the RS1 gene on Xp22.13. (arvojournals.org)
  • Induction
  • Pretreatment of cells with the p38MAPK-specific inhibitor SB202190 downregulates the induction of SOCS3-mRNA expression by IL-6. (uniprot.org)
  • These data indicate that p38MAPK-activation is crucial for IL-6-induced SOCS3 expression and downregulation of IL-6-mediated gene induction. (uniprot.org)
  • ELISA Kit
  • If you cannot find the target and/or product is not available in our catalog, please click here to contact us and request the product or submit your request for custom elisa kit production , custom recombinant protein production or custom antibody production . (mybiosource.com)
  • transcript variants
  • Alternatively spliced transcript variants of this gene have been identified, but the full-length nature of some of these variants has not been determined. (wikipedia.org)
  • These DNA primer pairs were designed by prioritizing the gene regions most commonly found in transcript variants. (bio-rad.com)
  • This gene has two different alternatively spliced transcript variants. (wikipedia.org)
  • inhibits
  • In vivo , CX-4945 inhibits activation of STAT-3, NF-κB p65, and AKT, and promotes survival of mice with intracranial human glioblastoma xenografts. (aacrjournals.org)
  • tumor
  • We use targeted conditional and inducible mouse models and other cellular and molecular approaches to uncover gene-expression and genomic and epigenetic alteration that occur during tumor development and progression and to functionally analyze the biological significance of these changes in oncogenic transformation. (stanford.edu)
  • TRIM32 additionally promotes cancer formation by ubiquitinating Abl-interactor 2 (Abi2), which is a tumor suppressor and inhibitor of cell migration. (wikipedia.org)
  • dimers
  • STAT molecules form dimers and bind to ISGF3G/IRF-9, which is Interferon stimulated gene factor 3 complex with Interferon regulatory Factor 9. (wikipedia.org)
  • Drosophila
  • During Drosophila research, it was found that a mutation in the gene MAD in the mother repressed the gene decapentaplegic in the embryo. (wikipedia.org)
  • intracellular
  • Indeed, drugs aimed at inhibiting Hsp90 have been shown to possess multiple intracellular targeting capacities and could potentially be active against many types of cancer through degradation of a large number of client proteins [ 4 ]. (ijbs.com)
  • catalytic
  • JAK3 inhibitors target the catalytic ATP-binding site of JAK3 and have there been various moieties utilised to get a stronger affinity and selectivity to the ATP-binding pockets. (wikipedia.org)
  • target
  • Our data suggest that combined treatment with Hsp90 inhibitor and SIRT1 inhibitor could be an effective therapeutic approach to target CSCs that are resistant to current therapies. (ijbs.com)
  • Heat shock protein 90 (Hsp90) has emerged as a major pharmaceutical target in cancer therapy, since Hsp90 is known to bind and stabilize a wide range of proteins with activity in the cell cycle, signal transduction and transcription, many of which are widely implicated in cancers [ 3 ]. (ijbs.com)
  • Each gene target within a pathway was assigned a score based on the frequency of differential expression and its research significance. (bio-rad.com)
  • This response is slower than the first because it involves more steps, like transcription of genes and then the effect of newly formed proteins in a specific target. (wikipedia.org)
  • The target could be a protein or another gene. (wikipedia.org)
  • GSK-3b mediates repression of CREB target genes in quiescent cells. (wikipedia.org)
  • Additionally
  • Additionally, TRIM32 is known to ubiquitinate dysbindin, a protein associated with both skeletal muscles and neural tissue. (wikipedia.org)
  • Additionally, an oral AXL inhibitor (TP-0903) is expected to enter Phase 1 clinical trial in November 2016 (in advanced solid tumours: NCT02729298). (wikipedia.org)
  • Hsp90
  • The current investigation was undertaken to examine the effectiveness of the combination treatment of Hsp90 inhibitor and SIRT1 inhibitor in inhibiting the growth of chemo-resistant stem-like cells isolated from human chronic myeloid leukemia K562 cells. (ijbs.com)
  • Moreover, 17-AAG-mediated activation of HSF1/Hsps and P-gp-mediated efflux, major causes of Hsp90 inhibitor resistance, was suppressed by SIRT1 inhibitor in K562-CD44 high cells. (ijbs.com)
  • bind
  • Hydrophobic/membrane-associated - are insoluble in water and membrane-associated, being localized at intermembrane spaces, where they can bind to membrane-associated effector proteins. (wikipedia.org)
  • induce
  • These results demonstrate that FLT3-ITD mutant proteins are sufficient to induce a myeloproliferative disorder, but are insufficient to recapitulate the AML phenotype observed in humans. (jove.com)