Identification of Degs in B Cells of Patients with Common Variable
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Peripheral T Cells Ets-1 Maintains IL-7 Receptor Expression In
The Journal of Immunology Ets-1 Maintains IL-7 Receptor Expression in Peripheral T Cells Roland Grenningloh,*,† Tzong-Shyuan Tai,* Nicole Frahm,†,‡,1 Tomoyuki C. Hongo,‡ Adam T. Chicoine,‡ Christian Brander,†,‡,x,{ Daniel E. Kaufmann,†,‡,‖ and I-Cheng Ho*,† The expression of CD127, the IL-7–binding subunit of the IL-7 R, is tightly regulated during the development and activation of T cells and is reduced during chronic viral infection. However, the molecular mechanism regulating the dynamic expression of CD127 is still poorly understood. In this study, we report that the transcription factor Ets-1 is required for maintaining the expression of CD127 in murine peripheral T cells. Ets-1 binds to and activates the CD127 promoter, and its absence leads to reduced CD127 expression, attenuated IL-7 signaling, and impaired IL-7–dependent homeostatic proliferation of T cells. The expression of CD127 and Ets-1 is strongly correlated in human T cells. Both CD127 and Ets-1 expression are decreased in CD8+ T cells during HIV infection. In addition, HIV-associated loss of CD127 is only observed in Ets-1low effector memory and central memory but not in Ets-1high naive CD8+ T cells. Taken together, our data identify Ets-1 as a critical regulator of CD127 expression in T cells. The Journal of Immunology, 2011, 186: 969–976. nterleukin-7 signals are required for T cell development, GABPa or another Ets protein is responsible for maintaining maintaining the naive T cell pool, mounting proper primary CD127 expression in peripheral T cells is unknown. I responses, and inducing and maintaining CD4+ and CD8+ Ets-1 (E26 transformation-specific sequence) is the founding T cell memory (1–3). -
Agonists and Knockdown of Estrogen Receptor Β Differentially Affect
Schüler-Toprak et al. BMC Cancer (2016) 16:951 DOI 10.1186/s12885-016-2973-y RESEARCH ARTICLE Open Access Agonists and knockdown of estrogen receptor β differentially affect invasion of triple-negative breast cancer cells in vitro Susanne Schüler-Toprak1*, Julia Häring1, Elisabeth C. Inwald1, Christoph Moehle2, Olaf Ortmann1 and Oliver Treeck1 Abstract Background: Estrogen receptor β (ERβ) is expressed in the majority of invasive breast cancer cases, irrespective of their subtype, including triple-negative breast cancer (TNBC). Thus, ERβ might be a potential target for therapy of this challenging cancer type. In this in vitro study, we examined the role of ERβ in invasion of two triple-negative breast cancer cell lines. Methods: MDA-MB-231 and HS578T breast cancer cells were treated with the specific ERβ agonists ERB-041, WAY200070, Liquiritigenin and 3β-Adiol. Knockdown of ERβ expression was performed by means of siRNA transfection. Effects on cellular invasion were assessed in vitro by means of a modified Boyden chamber assay. Transcriptome analyses were performed using Affymetrix Human Gene 1.0 ST microarrays. Pathway and gene network analyses were performed by means of Genomatix and Ingenuity Pathway Analysis software. Results: Invasiveness of MBA-MB-231 and HS578T breast cancer cells decreased after treatment with ERβ agonists ERB-041 and WAY200070. Agonists Liquiritigenin and 3β-Adiol only reduced invasion of MDA-MB-231 cells. Knockdown of ERβ expression increased invasiveness of MDA-MB-231 cells about 3-fold. Transcriptome and pathway analyses revealed that ERβ knockdown led to activation of TGFβ signalling and induced expression of a network of genes with functions in extracellular matrix, tumor cell invasion and vitamin D3 metabolism. -
Accompanies CD8 T Cell Effector Function Global DNA Methylation
Global DNA Methylation Remodeling Accompanies CD8 T Cell Effector Function Christopher D. Scharer, Benjamin G. Barwick, Benjamin A. Youngblood, Rafi Ahmed and Jeremy M. Boss This information is current as of October 1, 2021. J Immunol 2013; 191:3419-3429; Prepublished online 16 August 2013; doi: 10.4049/jimmunol.1301395 http://www.jimmunol.org/content/191/6/3419 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2013/08/20/jimmunol.130139 Material 5.DC1 References This article cites 81 articles, 25 of which you can access for free at: http://www.jimmunol.org/content/191/6/3419.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on October 1, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Global DNA Methylation Remodeling Accompanies CD8 T Cell Effector Function Christopher D. Scharer,* Benjamin G. Barwick,* Benjamin A. Youngblood,*,† Rafi Ahmed,*,† and Jeremy M. -
Genomic Interaction Between ER and HMGB2 Identifies DDX18 As A
Oncogene (2015) 34, 3871–3880 © 2015 Macmillan Publishers Limited All rights reserved 0950-9232/15 www.nature.com/onc ORIGINAL ARTICLE Genomic interaction between ER and HMGB2 identifies DDX18 as a novel driver of endocrine resistance in breast cancer cells AM Redmond1,2, C Byrne1, FT Bane1, GD Brown2, P Tibbitts1,KO’Brien1, ADK Hill1, JS Carroll2 and LS Young1 Breast cancer resistance to endocrine therapies such as tamoxifen and aromatase inhibitors is a significant clinical problem. Steroid receptor coactivator-1 (SRC-1), a coregulatory protein of the oestrogen receptor (ER), has previously been shown to have a significant role in the progression of breast cancer. The chromatin protein high mobility group box 2 (HMGB2) was identified as an SRC-1 interacting protein in the endocrine-resistant setting. We investigated the expression of HMGB2 in a cohort of 1068 breast cancer patients and found an association with increased disease-free survival time in patients treated with endocrine therapy. However, it was also verified that HMGB2 expression could be switched on in endocrine-resistant tumours from breast cancer patients. To explore the function of this poorly characterized protein, we performed HMGB2 ChIPseq and found distinct binding patterns between the two contexts. In the resistant setting, the HMGB2, SRC-1 and ER complex are enriched at promoter regions of target genes, with bioinformatic analysis indicating a switch in binding partners between the sensitive and resistant phenotypes. Integration of binding and gene expression data reveals a concise set of target genes of this complex including the RNA helicase DDX18. Modulation of DDX18 directly affects growth of tamoxifen-resistant cells, suggesting that it may be a critical downstream effector of the HMGB2:ER complex. -
ETS1, Nfkb and AP1 Synergistically Transactivate the Human GM ± CSF Promoter
Oncogene (1997) 14, 2845 ± 2855 1997 Stockton Press All rights reserved 0950 ± 9232/97 $12.00 ETS1, NFkB and AP1 synergistically transactivate the human GM ± CSF promoter Ross S Thomas1, Martin J Tymms1, Leigh H McKinlay1, M Frances Shannon2, Arun Seth3 and Ismarl Kola1 1Molecular Genetics and Development Group, Institute of Reproduction and Development, Monash University, Melbourne 3168, Australia; 2Division of Human Immunology, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide 5000, Australia; 3Department of Pathology, University of Toronto/Women's College Hospital, Toronto, Ontario, Canada Activation of helper T cells results in coordinate Activating signals ultimately result in cellular prolifera- expression of a number of cytokines involved in tion, and transcriptional induction and secretion of a dierentiation, proliferation and activation of the number of cytokines including IL-2 (interleukin-2), IL-3, haematopoietic system. Granulocyte-macrophage colony IFNg (interferon-gamma) and GM ± CSF (granulocyte- stimulating factor (GM ± CSF) is one such cytokine, macrophage colony-stimulating factor) (Stanley et al., whose increased expression results mostly from increases 1985; Miyajima et al., 1988; Arai et al., 1990). These in transcription. Cis-acting elements with NFkB, AP1 cytokines direct the eector functions of various cell and ETS-like binding motifs have been identi®ed in the types involved in an immune response, including B cells, promoter region of the GM ± CSF gene, and are macrophages, mast cells, eosinophils and neutrophils. important or essential for transcriptional activity follow- GM ± CSF expression in activated T cells is ing T cell activation. ETS1 is a transcription factor of regulated by two mechanisms. -
Id3 Induces an Elk-1- and Caspase-8-Dependent Apoptotic Pathway In
ID3 INDUCES AN ELK-1- AND CASPASE-8-DEPENDENT APOPTOTIC PATHWAY IN SQUAMOUS CARCINOMA CELLS A Dissertation submitted to the Faculty of the Graduate School of Arts and Sciences of Georgetown University in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biochemistry and Molecular & Cellular Biology By You-shin Chen, M.S. Washington, DC November 18, 2014 Copyright 2014 by You-shin Chen All Rights Reserved ii ID3 INDUCES AN ELK-1- AND CASPASE-8-DEPENDENT APOPTOTIC PATHWAY IN SQUAMOUS CARCINOMA CELLS You-shin Chen, M.S. Thesis Advisor: Dean S. Rosenthal, Ph.D. ABSTRACT Inhibitors of differentiation/DNA binding (Id) proteins are helix-loop-helix (HLH) transcription factors. The Id protein family (Id1-Id4) mediates tissue homeostasis by regulating cellular processes including differentiation, proliferation, and apoptosis. Previously, we found that Id3 induced apoptosis in immortalized human keratinocytes (Simbulan-Rosenthal et al., 2006), consistent with its role as a tumor suppressor (Richter et al., 2012; Schmitz et al., 2012). To investigate the role of Id3 in malignant SCC cells (A431), a tetracycline-regulated inducible system was used to induce Id3 in cell culture and mouse xenograft models. We found that upon Id3 induction, there was a decrease in cell number under low serum conditions, as well as in soft agar. Microarray, RT-PCR, immunoblot, siRNA, and inhibitor studies revealed that Id3 induced expression of Elk-1, an ETS-domain transcription factor, inducing procaspase-8 expression and activation. Id3 deletion mutants revealed that 80 C-terminal amino acids, including the HLH, are important for Id3-induced apoptosis. -
FOXP1 Acts Through a Negative Feedback Loop to Suppress FOXO-Induced Apoptosis
Cell Death and Differentiation (2013) 20, 1219–1229 & 2013 Macmillan Publishers Limited All rights reserved 1350-9047/13 www.nature.com/cdd FOXP1 acts through a negative feedback loop to suppress FOXO-induced apoptosis R van Boxtel1,5, C Gomez-Puerto1,6, M Mokry2,6, A Eijkelenboom3, KE van der Vos1, EES Nieuwenhuis2, BMT Burgering3, EW-F Lam4 and PJ Coffer*,1,2 Transcriptional activity of Forkhead box transcription factor class O (FOXO) proteins can result in a variety of cellular outcomes depending on cell type and activating stimulus. These transcription factors are negatively regulated by the phosphoinositol 3-kinase (PI3K)–protein kinase B (PKB) signaling pathway, which is thought to have a pivotal role in regulating survival of tumor cells in a variety of cancers. Recently, it has become clear that FOXO proteins can promote resistance to anti-cancer therapeutics, designed to inhibit PI3K–PKB activity, by inducing the expression of proteins that provide feedback at different levels of this pathway. We questioned whether such a feedback mechanism may also exist directly at the level of FOXO-induced transcription. To identify critical modulators of FOXO transcriptional output, we performed gene expression analyses after conditional activation of key components of the PI3K–PKB–FOXO signaling pathway and identified FOXP1 as a direct FOXO transcriptional target. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that FOXP1 binds enhancers that are pre-occupied by FOXO3. By sequencing the transcriptomes of cells in which FOXO is specifically activated in the absence of FOXP1, we demonstrate that FOXP1 can modulate the expression of a specific subset of FOXO target genes, including inhibiting expression of the pro-apoptotic gene BIK. -
Supplemental Text and Figures
Supplemental Materials and Methods Experimental bone metastasis assay Primary PCa cells were sorted by GFP marker from mTmG+ tumors, and 105 cells in 20μL PBS were injected using Hamilton syringe into the tibia of 6-week old NSG mice. Mice were monitored biweekly for moribund signs for euthanasia and organ harvest. Noninvasive mouse and ex vivo imaging MRI imaging with Bruker ICON and fluorescence imaging of fresh organs with metastasis enumeration were recently described (Lu et al. 2017). Primary prostate cell sphere formation assay Isolate of primary cells from prostate, culture and counting of prostatospheres on Matrigel were performed as described (Lukacs et al. 2010). For organoid culture assay, we followed a published matrigel embedding method (Chua et al. 2014). RNA-Seq and differential gene expression Total RNA was isolated from prostate tumors using Direct-zol RNA MiniPrep Kit (Zymo Research) and processed for stranded total RNA-Seq using Illumina HiSeq 4000 at Sequencing and Microarray Facility at MD Anderson Cancer Center. The differential expression analysis was performed using the DESeq2 package of R. P-values obtained after multiple binomial tests were adjusted using BH method. Significant genes are defined by using a cut-off of 0.05 on the BH corrected p-value and an absolute log2 fold change value of at least 1.5. Histology and western blot H&E stain, immunohistochemical (IHC) and western blot were performed as previously described (Ding et al. 2011; Wang et al. 2016). Primary antibodies for IHC include Ki67 (Fisher, RM-9106-S1), cleaved caspase 3 (Cell Signaling Technology aka CST, 9661), cyclin D1 (Fisher, clone SP4), TGFBR2 (Abcam, ab61213), BMPR2 (Abcam, ab130206), AR (EMD Millipore, 06-680), phospho- Akt (CST, 4060), GFP (CST, 2956), E-Cadherin (CST, 14472). -
Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells
This is an electronic reprint of the original article. This reprint may differ from the original in pagination and typographic detail. Ubaid Ullah, Ullah; Andrabi, Syed Bilal Ahmad; Tripathi, Subhash Kumar; Dirasantha, Obaiah; Kanduri, Kartiek; Rautio, Sini; Gross, Catharina C.; Lehtimäki, Sari; Bala, Kanchan; Tuomisto, Johanna; Bhatia, Urvashi; Chakroborty, Deepankar; Elo, Laura L.; Lähdesmäki, Harri; Wiendl, Heinz; Rasool, Omid; Lahesmaa, Riitta Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells Published in: Cell Reports DOI: 10.1016/j.celrep.2018.01.070 Published: 20/02/2018 Document Version Publisher's PDF, also known as Version of record Published under the following license: CC BY-NC-ND Please cite the original version: Ubaid Ullah, U., Andrabi, S. B. A., Tripathi, S. K., Dirasantha, O., Kanduri, K., Rautio, S., Gross, C. C., Lehtimäki, S., Bala, K., Tuomisto, J., Bhatia, U., Chakroborty, D., Elo, L. L., Lähdesmäki, H., Wiendl, H., Rasool, O., & Lahesmaa, R. (2018). Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells. Cell Reports, 22(8), 2094-2106. https://doi.org/10.1016/j.celrep.2018.01.070 This material is protected by copyright and other intellectual property rights, and duplication or sale of all or part of any of the repository collections is not permitted, except that material may be duplicated by you for your research use or educational purposes in electronic or print form. You must obtain permission for any other use. Electronic or print copies may not be offered, whether for sale or otherwise to anyone who is not an authorised user. -
Rs1944919 on Chromosome 11Q23.1 and Its Effector Genes COLCA1
www.nature.com/scientificreports OPEN rs1944919 on chromosome 11q23.1 and its efector genes COLCA1/COLCA2 confer susceptibility to primary biliary cholangitis Yuki Hitomi1*, Yoshihiro Aiba2, Yosuke Kawai3, Kaname Kojima4, Kazuko Ueno3, Nao Nishida3,5, Minae Kawashima6, Olivier Gervais7, Seik‑Soon Khor3, Masao Nagasaki7, Katsushi Tokunaga3, Minoru Nakamura2,8,9 & Makoto Tsuiji1* Primary biliary cholangitis (PBC) is a chronic, progressive cholestatic liver disease in which intrahepatic bile ducts are destroyed by an autoimmune reaction. Our previous genome‑wide association study (GWAS) identifed chromosome 11q23.1 as a susceptibility gene locus for PBC in the Japanese population. Here, high‑density association mapping based on single nucleotide polymorphism (SNP) imputation and in silico/in vitro functional analyses identifed rs1944919 as the primary functional variant. Expression‑quantitative trait loci analyses showed that the PBC susceptibility allele of rs1944919 was signifcantly associated with increased COLCA1/COLCA2 expression levels. Additionally, the efects of rs1944919 on COLCA1/COLCA2 expression levels were confrmed using genotype knock‑in versions of cell lines constructed using the CRISPR/Cas9 system and difered between rs1944919‑G/G clones and ‑T/T clones. To our knowledge, this is the frst study to demonstrate the contribution of COLCA1/COLCA2 to PBC susceptibility. Primary biliary cholangitis (PBC) is a chronic, progressive cholestatic liver disease in which intrahepatic small bile ducts are destroyed. PBC is considered an organ-specifc autoimmune disease for the following reasons: (1) existence of autoreactive T and B cells from PBC patients and well-defned autoantigens such as the E2 com- ponent of the pyruvate dehydrogenase complex, (2) high frequencies of complications of other autoimmune diseases, (3) overlap of many disease susceptibility gene loci with those of other autoimmune diseases, and (4) an overwhelming female predominance 1–5. -
Rabbit Anti-SIAH1/FITC Conjugated Antibody-SL3596R-FITC
SunLong Biotech Co.,LTD Tel: 0086-571- 56623320 Fax:0086-571- 56623318 E-mail:[email protected] www.sunlongbiotech.com Rabbit Anti-SIAH1/FITC Conjugated antibody SL3596R-FITC Product Name: Anti-SIAH1/FITC Chinese Name: FITC标记的Ubiquitin连接酶Siah1抗体 hSIAH1; HUMSIAH; Seven in absentia homolog 1 (Drosophila); Seven in absentia homolog 1; Siah 1; Siah 1a; Ubiquitin ligase SIAH1; E3 ubiquitin-protein ligase SIAH1; Alias: Seven in absentia homolog 1; Siah-1; Siah-1a; Siah E3 ubiquitin protein ligase 1; SIAH1_HUMAN; SIAH1A. Organism Species: Rabbit Clonality: Polyclonal React Species: Human,Mouse,Rat,Chicken,Dog,Pig,Cow,Horse,Rabbit, IF=1:50-200 Applications: not yet tested in other applications. optimal dilutions/concentrations should be determined by the end user. Molecular weight: 34kDa Form: Lyophilized or Liquid Concentration: 1mg/ml immunogen: KLH conjugated synthetic peptide derived from human SIAH1 Lsotype: IgG Purification: affinitywww.sunlongbiotech.com purified by Protein A Storage Buffer: 0.01M TBS(pH7.4) with 1% BSA, 0.03% Proclin300 and 50% Glycerol. Store at -20 °C for one year. Avoid repeated freeze/thaw cycles. The lyophilized antibody is stable at room temperature for at least one month and for greater than a year Storage: when kept at -20°C. When reconstituted in sterile pH 7.4 0.01M PBS or diluent of antibody the antibody is stable for at least two weeks at 2-4 °C. background: This gene encodes a protein that is a member of the seven in absentia homolog (SIAH) family. The protein is an E3 ligase and is involved in ubiquitination and proteasome- Product Detail: mediated degradation of specific proteins. -
BOB1 (POU2AF1) Rabbit Polyclonal Antibody – TA590578 | Origene
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA590578 BOB1 (POU2AF1) Rabbit Polyclonal Antibody Product data: Product Type: Primary Antibodies Applications: ELISA, WB Recommended Dilution: WB 1:5000~20000,ELISA 1:100-1:2000 Reactivity: Human Host: Rabbit Isotype: IgG Clonality: Polyclonal Immunogen: DNA immunization. This antibody is specific for the C Terminus Region of the target protein. Formulation: 20 mM Potassium Phosphate, 150 mM Sodium Chloride, pH 7.0 Concentration: 1 mg/ml Purification: Purified from mouse ascites fluids or tissue culture supernatant by affinity chromatography (protein A/G) Conjugation: Unconjugated Storage: Store at -20°C as received. Stability: Stable for 12 months from date of receipt. Gene Name: POU class 2 homeobox associating factor 1 Database Link: NP_006226 Entrez Gene 5450 Human Q16633 Background: A novel 35kDa protein designated Bob1 (B cell Oct binding protein 1) is a lymphocyte specific transcription co activator protein. B cell specific transcription is mediated by octamer motifs found in immunoglobulin heavy and light chain gene promoters and in some immunoglobulin enhancers. These sites are bound by the B cell specific Oct1 and Oct2 transcription factors, and the B cell restricted co activator BOB.1/OBF.1. This protein interacts only with the Oct1/2 proteins through sub domains in the POU domain of the Oct1/2 proteins, enhancing their transcriptional efficacy. Although having no intrinsic capacity for DNA binding, Bob1 associates tightly with the octomer motif in the presence of Oct1 and Oct2.