20 research outputs found
Ets-2 and C/EBP-beta are important mediators of ovine trophoblast Kunitz domain protein-1 gene expression in trophoblast
BACKGROUND: The trophoblast Kunitz domain proteins (TKDPs) constitute a highly expressed, placenta-specific, multigene family restricted to ruminant ungulates and characterized by a C-terminal "Kunitz" domain, preceded by one or more unique N-terminal domains. TKDP-1 shares an almost identical expression pattern with interferon-tau, the "maternal recognition of pregnancy protein" in ruminants. Our goal here has been to determine whether the ovine (ov) Tkdp-1 and IFNT genes possess a similar transcriptional code. RESULTS: The ovTkdp-1 promoter has been cloned and characterized. As with the IFNT promoter, the Tkdp-1 promoter is responsive to Ets-2, and promoter-driven reporter activity can be increased over 700-fold in response to over-expression of Ets-2 and a constitutively active form of protein Kinase A (PKA). Unexpectedly, the promoter element of Tkdp-1 responsible for this up-regulation, unlike that of the IFNT, does not bind Ets-2. However, mutation of a CCAAT/enhancer binding element within this control region not only reduced basal transcriptional activity, but prevented Ets-2 as well as cyclic adenosine 5'-monophosphate (cAMP)/PKA and Ras/mitogen-activated protein kinase (MAPK) responsiveness. In vitro binding experiments and in vivo protein-protein interaction assays implicated CCAAT/enhancer binding protein-beta (C/EBP-β) as involved in up-regulating the Tkdp-1 promoter activity. A combination of Ets-2 and C/EBP-β can up-regulate expression of the minimal Tkdp-1 promoter as much as 930-fold in presence of a cAMP analog. An AP-1-like element adjacent to the CCAAT enhancer, which binds Jun family members, is required for basal and cAMP/ C/EBP-β-dependent activation of the gene, but not for Ets-2-dependent activity. CONCLUSION: This paper demonstrates how Ets-2, a key transcription factor for trophoblast differentiation and function, can control expression of two genes (Tkdp-1 and IFNT) having similar spatial and temporal expression patterns via very different mechanisms
Novel 3-dimensional sixfold interpenetrating diamondoid networks of copper(I) coordination polymers of polypyridyl ligands - Syntheses,characterization and crystal structures
Two new coordination polymers [Cu(L-1)(2)](n)(ClO4)(n)center dot 2nH(2)O (1), [Cu(L-2)(2)](n)(ClO4)(n)center dot 2nH(2)O (2) of polydentate imine/pyridyl ligands, L-1 and L-2 with Cu(I) ion have been synthesized and characterized by single crystal X-ray diffraction studies, elemental analyses, IR' UV-vis and NMR spectroscopy. They represent 3-dimensional, sixfold interpenetrating diamondoid network structures having large pores of dimension, 35 x 21 angstrom(2) in 1 and 38 x 19 angstrom(2) in 2, respectively
The syntheses, characterizations, X-ray crystal structures and properties of Cu(I) complexes of a bis-bidentate schiff base ligand
Bis-bidentate Schiff base ligand L and its two mononuclear complexes [CuL(CH3CN)(2)]ClO4 (1)and [CuL(PPh3)(2)]ClO4 (2)have been prepared and thoroughly characterized by elemental analyses, IR, UV-Vis, NMR spectroscopy and X-ray diffraction analysis. In both the complexes the metal ion auxiliaries adopt tetrahedral coordination environment. Their reactivity, electrochemical and photophysical behavior have been studied. Complex 1 shows reversible Cu-II/I couple with potential 0.74 V versus Ag/AgCl in CH2Cl2. At room temperature L is weakly fluorescent in CH2Cl2, however in Cu(I)complexes 1 and 2 the emission in quenched. (C) 2009 Elsevier B. V. All rights reserved
The syntheses, characterizations, X-ray crystal structures and properties of Cu(I) complexes of a bis-bidentate schiff base ligand
Bis-bidentate Schiff base ligand L and its two mononuclear complexes [CuL(CH3CN)(2)]ClO4 (1)and [CuL(PPh3)(2)]ClO4 (2)have been prepared and thoroughly characterized by elemental analyses, IR, UV-Vis, NMR spectroscopy and X-ray diffraction analysis. In both the complexes the metal ion auxiliaries adopt tetrahedral coordination environment. Their reactivity, electrochemical and photophysical behavior have been studied. Complex 1 shows reversible Cu-II/I couple with potential 0.74 V versus Ag/AgCl in CH2Cl2. At room temperature L is weakly fluorescent in CH2Cl2, however in Cu(I)complexes 1 and 2 the emission in quenched. (C) 2009 Elsevier B. V. All rights reserved
<b>Opposing Interplay between Nuclear Factor Erythroid 2‑Related Factor 2 and Forkhead BoxO 1/3 is Responsible for Sepantronium Bromide’s Poor Efficacy and Resistance in Cancer cells: Opportunity for Combination Therapy in Triple Negative Breast Cancer</b>
Survivin,
a cancer-cell-specific multifunctional protein,
is regulated
by many oncogenic signaling pathways and an effective therapeutic
target. Although, several types of survivin-targeting agents have
been developed over the past few decades, none of them received clinical
approval. This could be because survivin expression is tightly controlled
by the feedback interaction between different signaling molecules.
Of the several signaling pathways that are known to regulate survivin
expression, the phosphatidylinositol 3-kinase/AKT serine-threonine
kinase/forkhead boxO (PI3K/AKT/FoxO) pathway is well-known for feedback
loops constructed by cross-talk among different molecules. Using sepantronium
bromide (YM155), the first of its class of survivin-suppressant, we
uncovered the existence of an interesting cross-talk between Nuclear
Factor Erythroid 2-Related Factor 2 (NRF2) and FoxO transcription
factors that also contributes to YM155 resistance in triple negative
breast cancer (TNBC) cells. Pharmacological manipulation to interrupt
this interaction not only helped restore/enhance the drug-sensitivity
but also prompted effective immune clearance of cancer cells. Because
the YM155-induced reactive oxygen species (ROS) initiates this feedback,
we believe that it will be occurring for many ROS-producing chemotherapeutic
agents. Our work provides a rational explanation for the poor efficacy
of YM155 compared to standard chemotherapy in clinical trials. Finally,
the triple drug combination approach used herein might help reintroducing
YM155 into the clinical pipeline, and given the high survivin expression
in TNBC cells in general, it could be effective in treating this subtype
of breast cancer