Search results for "T1"
showing 10 items of 587 documents
Role of myeloïd derived suppressive cells (MDSC) and Th17 lymphocytes in chemotherapy and immunotherapy efficacy
2017
Actual oncology is still facing resistance and rapid progression of cancer. Intrinsic resistance mechanisms developed by tumor cells determine chemotherapy and immunotherapy efficacy. It is now recognized that the host immune response status is in part implicated in the therapeutic outcome of patients. The aim of our research team is to characterize this response and to study the impact of therapies in order to identify the mechanisms associated with future exhaust of the tumor. In this context, we have shown that chemotherapy (5-FU, oxaliplatin, anti-VEGF: FOLFOX-bevacizumab) in some patients causes a drop in devices gMDSC (granulocytic myeloid derived suppressive cells) that is associated…
Selective Inhibition of STAT3 with Respect to STAT1: Insights from Molecular Dynamics and Ensemble Docking Simulations
2016
STAT3 protein, which is known to be involved in cancer development, is a promising target for anticancer therapy. Successful inhibitors of STAT3 should not affect an activity of closely related protein STAT1, which makes their development challenging. The mechanisms of selectivity of several existing STAT3 inhibitors are not clear. In this work, we studied molecular mechanisms of selectivity of 13 experimentally tested STAT3 inhibitors by means of extensive molecular dynamics and ensemble docking simulations. It is shown that all studied inhibitors bind to the large part of the protein surface in an unspecific statistical manner. The binding to the dimerization interface of the SH2 domain, …
Cytoplasmic STAT proteins associate prior to activation
2000
The commonly accepted model of STAT factor activation at the cytoplasmic part of the receptor assumes that signal transducers and activators of transcription (STATs) are recruited from a cytoplasmic pool of monomeric STAT proteins. Based on a previous observation that non-phosphorylated STAT3-Src homology 2 domains dimerize in vitro, we investigated whether the observed dimerization is of physiological relevance within the cellular context. We show that STAT1 and STAT3 are pre-associated in non-stimulated cells. Apparently, these complexes are not able to translocate into the nucleus. We provide evidence that the event of STAT activation is more complex than previously assumed.
Inhibition of Ulcerative Colitis in Mice after Oral Administration of a Polyphenol-Enriched Cocoa Extract Is Mediated by the Inhibition of STAT1 and …
2011
We studied a polyphenol-enriched cocoa extract (PCE) with epicatechin, procyanidin B2, catechin, and procyanidin B1 as the major phenolics for its anti-inflammatory properties against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. PCE reduced colon damage, with significant reductions in both the extent and the severity of the inflammation as well as in crypt damage and leukocyte infiltration in the mucosa. Analysis ex vivo showed clear decreases in the production of nitric oxide, cyclooxygenase-2, pSTAT-3, and pSTAT1α, with NF-κB p65 production being slightly reduced. Moreover, NF-κB activation was reduced in RAW 264.7 cells in vitro. In conclusion, the inhibitory eff…
The interleukin-22/STAT3 pathway potentiates expression of inducible nitric-oxide synthase in human colon carcinoma cells.
2007
Inducible nitric-oxide synthase (iNOS) has been identified as a marker and mediator of disease in human colonic inflammation and carcinogenesis. Accordingly, identification of mediators that trigger iNOS in colon carcinoma/epithelial cells is an important topic of current research. Here we demonstrate that interleukin (IL)-22, a newly described member of the IL-10 cytokine family, potently synergizes with interferon (IFN)-gamma for iNOS expression in human DLD-1 colon carcinoma cells. Detection of both IL-22 receptor chains and STAT3 phosphorylation proved robust IL-22 responsiveness of these cells. Short interfering RNA technology identified STAT3 as being crucial for up-regulation of iNOS…
HAT1 and HAT2 Proteins Are Components of a Yeast Nuclear Histone Acetyltransferase Enzyme Specific for Free Histone H4
1998
We have analyzed the histone acetyltransferase enzymes obtained from a series of yeast hat1, hat2, and gcn5 single mutants and hat1,hat2 and hat1,gcn5 double mutants. Extracts prepared from both hat1 and hat2 mutant strains specifically lack the following two histone acetyltransferase activities: the well known cytoplasmic type B enzyme and a free histone H4-specific histone acetyltransferase located in the nucleus. The catalytic subunits of both cytoplasmic and nuclear enzymes have identical molecular masses (42 kDa), the same as that of HAT1. However, the cytoplasmic complex has a molecular mass (150 kDa) greater than that of the nuclear complex (110 kDa). The possible functions of HAT1 a…
Regulation of mating in the budding yeast Saccharomyces cerevisiae by the zinc cluster proteins Sut1 and Sut2
2013
This article is made available through the Brunel Open Access Publishing Fund. Copyright @ The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The zinc cluster proteins Sut1 and Sut2 play a role in sterol uptake and filamentous growth in the budding yeast Saccharomyces cerevisiae. In this study, we show that they are also involved in mating. Cells that lack both SUT1 and SUT2 were defective in mating. The expression of the genes NCE102 and PRR2 was increased in the sut1 sut2 double deletion mutant…
Yeast HAT1 and HAT2 deletions have different life-span and transcriptome phenotypes
2005
AbstractHAT-B is a yeast histone acetyltransferase composed of Hat1, Hat2 and Hif1 proteins. We demonstrate that a hat2 mutant or a hat1hat2 double mutant, but not a hat1 mutant, have an extended life-span. Transcriptome analysis shows that the single hat mutants are not very different from wild type. However, the comparison of the hat1 and hat2 transcriptomes shows that they are different. The hat1hat2 double mutant shows a transcriptional phenotype similar to that of the hat1 mutant but strongly enhanced. These results indicate that Hat2p could have additional functions in the cell to those of Hat1p.
Hif1 Is a Component of Yeast Histone Acetyltransferase B, a Complex Mainly Localized in the Nucleus
2004
Hat1 is the catalytic subunit of the only type B histone acetyltransferase known (HAT-B). The enzyme specifically acetylates lysine 12, and to a lesser extent lysine 5, of free, non-chromatin-bound histone H4. The complex is usually isolated with cytosolic fractions and is thought to be involved in chromatin assembly. The Saccharomyces cerevisiae HAT-B complex also contains Hat2, a protein stimulating Hat1 catalytic activity. We have now identified by two-hybrid experiments Hif1 as both a Hat1- and a histone H4-interacting protein. These interactions were dependent on HAT2, indicating a mediating role for Hat2. Biochemical fractionation and co-immunoprecipitation assays demonstrated that Hi…
Cytotoxic Acacic Acid Glycosides from the Roots of Albizia coriaria
2009
Two new oleanane-type saponins, coriariosides A (1) and B (2), along with a known saponin, gummiferaoside C (3), were isolated from the roots of Albizia coriaria. Their structures were established by extensive analysis of 1D and 2D NMR experiments (COSY, ROESY, TOCSY, HSQC, and HMBC) and mass spectrometry. Compounds 1 and 3 when tested for cytotoxicity against two colorectal human cancer cells showed activity against the HCT 116 (IC50 4.2 microM for 1 and 2.7 microM for 3) and HT-29 (IC50 6.7 microM for 1 and 7.9 microM for 3) cell lines.