Genomes and Genes
ccaat enhancer binding proteins
Summary: A class of proteins that were originally identified by their ability to bind the DNA sequence CCAAT. The typical CCAAT-enhancer binding protein forms dimers and consists of an activation domain, a DNA-binding basic region, and a leucine-rich dimerization domain (LEUCINE ZIPPERS). CCAAT-BINDING FACTOR is structurally distinct type of CCAAT-enhancer binding protein consisting of a trimer of three different subunits.
- Sourisseau T, Georgiadis A, Tsapara A, Ali R, Pestell R, Matter K, et al. Regulation of PCNA and cyclin D1 expression and epithelial morphogenesis by the ZO-1-regulated transcription factor ZONAB/DbpA. Mol Cell Biol. 2006;26:2387-98 pubmed
- Lorenzato M, Caudroy S, Bronner C, Evrard G, Simon M, Durlach A, et al. Cell cycle and/or proliferation markers: what is the best method to discriminate cervical high-grade lesions?. Hum Pathol. 2005;36:1101-7 pubmed..8% and 74.3%. Thus, the most accurate test to distinguish an LSIL from an HSIL was the association of a suspect DNA profile and the presence of MIB-1- or ICBP90-positive cells in the upper two thirds of the epithelium. ..
- Jenkins Y, Markovtsov V, Lang W, Sharma P, Pearsall D, Warner J, et al. Critical role of the ubiquitin ligase activity of UHRF1, a nuclear RING finger protein, in tumor cell growth. Mol Biol Cell. 2005;16:5621-9 pubmed..Taken together, our results suggest a general requirement for UHRF1 in tumor cell proliferation and implicate the RING domain of UHRF1 as a functional determinant of growth regulation. ..
- Tobita H, Kajino K, Inami K, Kano S, Yasen M, Imamura O, et al. Gene expression profile of DNA binding protein A transgenic mice. Int J Oncol. 2006;29:673-9 pubmed..In conclusion, our present data suggested that dbpA could be positively involved in carcinogenesis by changing the expression profiles of cellular genes. ..
- Wouters B, Louwers I, Valk P, Lowenberg B, Delwel R. A recurrent in-frame insertion in a CEBPA transactivation domain is a polymorphism rather than a mutation that does not affect gene expression profiling-based clustering of AML. Blood. 2007;109:389-90 pubmed
- Starz Gaiano M, Melani M, Wang X, Meinhardt H, Montell D. Feedback inhibition of Jak/STAT signaling by apontic is required to limit an invasive cell population. Dev Cell. 2008;14:726-38 pubmed publisher..These findings are supported by a mathematical model, which accurately simulates wild-type and mutant phenotypes. ..
- Avvakumov G, Walker J, Xue S, Li Y, Duan S, Bronner C, et al. Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1. Nature. 2008;455:822-5 pubmed publisher..The structure, along with mutagenesis data, suggests how UHRF1 acts as a key factor for DNMT1 maintenance methylation through recognition of a fundamental unit of epigenetic inheritance, mCpG. ..
- Achour M, Jacq X, Ronde P, Alhosin M, Charlot C, Chataigneau T, et al. The interaction of the SRA domain of ICBP90 with a novel domain of DNMT1 is involved in the regulation of VEGF gene expression. Oncogene. 2008;27:2187-97 pubmed..They further suggest a new role of ICBP90 in the relationship between histone ubiquitination and DNA methylation in the context of tumoral angiogenesis and tumour suppressor genes silencing. ..
- Achour M, Fuhrmann G, Alhosin M, Ronde P, Chataigneau T, Mousli M, et al. UHRF1 recruits the histone acetyltransferase Tip60 and controls its expression and activity. Biochem Biophys Res Commun. 2009;390:523-8 pubmed publisher..Altogether, these results suggest that Tip60 is a novel partner of the epigenetic integration platform interplayed by UHRF1, DNMT1 and HDAC1 involved in the epigenetic code replication. ..
- Meilinger D, Fellinger K, Bultmann S, Rothbauer U, Bonapace I, Klinkert W, et al. Np95 interacts with de novo DNA methyltransferases, Dnmt3a and Dnmt3b, and mediates epigenetic silencing of the viral CMV promoter in embryonic stem cells. EMBO Rep. 2009;10:1259-64 pubmed publisher..Our results indicate a regulatory role for Np95, Dnmt3a and Dnmt3b in mediating epigenetic silencing through histone modification followed by DNA methylation. ..
- Kim J, Esteve P, Jacobsen S, Pradhan S. UHRF1 binds G9a and participates in p21 transcriptional regulation in mammalian cells. Nucleic Acids Res. 2009;37:493-505 pubmed publisher..Thus, our results suggest that UHRF1 may serve as a focal point of transcriptional regulation mediated by G9a and other chromatin modification enzymes. ..
- Bronner C, Achour M, Arima Y, Chataigneau T, Saya H, Schini Kerth V. The UHRF family: oncogenes that are drugable targets for cancer therapy in the near future?. Pharmacol Ther. 2007;115:419-34 pubmed..Alteration of these regulatory mechanisms, such as those occurring in cancer cells, may be involved in carcinogenesis. The reasons why the UHRF family could be an interesting target for developing anticancer drugs is also developed. ..
- Qian C, Li S, Jakoncic J, Zeng L, Walsh M, Zhou M. Structure and hemimethylated CpG binding of the SRA domain from human UHRF1. J Biol Chem. 2008;283:34490-4 pubmed publisher..Using NMR structure-guided mutagenesis, electrophoretic mobility shift assay, and fluorescence anisotropy analysis, we determined key amino acid residues for methyl-DNA binding that are conserved in the SRA domain. ..
- Wang X, Bo J, Bridges T, Dugan K, Pan T, Chodosh L, et al. Analysis of cell migration using whole-genome expression profiling of migratory cells in the Drosophila ovary. Dev Cell. 2006;10:483-95 pubmed..Functional analysis revealed a role for the Notch-activating protease Kuzbanian in border cell migration and identified Tie as a guidance receptor for the border cells. ..
- Bostick M, Kim J, Esteve P, Clark A, Pradhan S, Jacobsen S. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science. 2007;317:1760-4 pubmed..These data suggest that UHRF1 may help recruit DNMT1 to hemimethylated DNA to facilitate faithful maintenance of DNA methylation. ..
- Gaidzik V, Dohner K. Prognostic implications of gene mutations in acute myeloid leukemia with normal cytogenetics. Semin Oncol. 2008;35:346-55 pubmed publisher..Furthermore, these mutant molecules represent potential targets for molecular therapies. ..
- Oishi Y, Manabe I, Tobe K, Tsushima K, Shindo T, Fujiu K, et al. Krüppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation. Cell Metab. 2005;1:27-39 pubmed..KLF5, in turn, acts in concert with C/EBPbeta/delta to activate the PPARgamma2 promoter. This study establishes KLF5 as a key component of the transcription factor network controlling adipocyte differentiation. ..
- Jeanblanc M, Mousli M, Hopfner R, Bathami K, Martinet N, Abbady A, et al. The retinoblastoma gene and its product are targeted by ICBP90: a key mechanism in the G1/S transition during the cell cycle. Oncogene. 2005;24:7337-45 pubmed..We propose that ICBP90 overexpression, found in cancer cells, is involved in the altered checkpoint controls occurring in cancerogenesis. ..
- Karagianni P, Amazit L, Qin J, Wong J. ICBP90, a novel methyl K9 H3 binding protein linking protein ubiquitination with heterochromatin formation. Mol Cell Biol. 2008;28:705-17 pubmed..Furthermore, we present evidence that ICBP90 is required for proper heterochromatin formation in mammalian cells. ..
- Macaluso M, Montanari M, Noto P, Gregorio V, Bronner C, Giordano A. Epigenetic modulation of estrogen receptor-alpha by pRb family proteins: a novel mechanism in breast cancer. Cancer Res. 2007;67:7731-7 pubmed
- Abbady A, Bronner C, Bathami K, Muller C, Jeanblanc M, Mathieu E, et al. TCR pathway involves ICBP90 gene down-regulation via E2F binding sites. Biochem Pharmacol. 2005;70:570-9 pubmed..Altogether, our data demonstrate that TCR signaling pathways regulate ICBP90 gene expression through pRb/E2F complex. We propose that ICBP90 down-regulation is a key event in G1 arrest preceding T cell death. ..
- Nerlov C. The C/EBP family of transcription factors: a paradigm for interaction between gene expression and proliferation control. Trends Cell Biol. 2007;17:318-24 pubmed..More recently, their position at the crossroads between proliferation and differentiation has made them strong candidate regulators of tumorigenesis, and C/EBPs have been described as both tumor promoters and tumor suppressors. ..
- Marcucci G, Maharry K, Radmacher M, Mrozek K, Vukosavljevic T, Paschka P, et al. Prognostic significance of, and gene and microRNA expression signatures associated with, CEBPA mutations in cytogenetically normal acute myeloid leukemia with high-risk molecular features: a Cancer and Leukemia Group B Study. J Clin Oncol. 2008;26:5078-87 pubmed publisher..The gene and miRNA expression profiling provided insights into leukemogenesis of the CN-AML molecular high-risk group, indicating that CEBPA mutations are associated with partial erythroid differentiation. ..
- You M, Crabb D. Molecular mechanisms of alcoholic fatty liver: role of sterol regulatory element-binding proteins. Alcohol. 2004;34:39-43 pubmed..Consistent with this hypothesis, chronic ethanol feeding (4 weeks) resulted in a significantly reduced activity and protein level of AMP-activated protein kinase and increased acetyl coenzyme A carboxylase activity in the mouse livers. ..
- Dinic S, Ivanovic Matic S, Mihailovic M, Bogojevic D, Poznanovic G. Expression of C/EBP delta in rat liver during development and the acute-phase response. Gen Physiol Biophys. 2004;23:499-504 pubmed..2002). The obtained different solubility partitioning profiles of C/EBP delta suggest that its activity is regulated by different mechanisms during development and in the adult. ..
- Mori T, Sakaue H, Iguchi H, Gomi H, Okada Y, Takashima Y, et al. Role of Krüppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis. J Biol Chem. 2005;280:12867-75 pubmed..Our observations thus demonstrate that KLF15 plays an essential role in adipogenesis in 3T3-L1 cells through its regulation of PPAR gamma expression. ..
- Westmacott A, Burke Z, Oliver G, Slack J, Tosh D. C/EBPalpha and C/EBPbeta are markers of early liver development. Int J Dev Biol. 2006;50:653-7 pubmed..Both are complementary to the early expression of Pdx1, a key pancreatic transcription factor. These results are consistent with the idea that C/EBP factors are master regulators for liver development. ..
- Dubois S, Heilbronn L, Smith S, Albu J, Kelley D, Ravussin E. Decreased expression of adipogenic genes in obese subjects with type 2 diabetes. Obesity (Silver Spring). 2006;14:1543-52 pubmed..07). This cross-sectional study supports the hypothesis that impaired expression of adipogenic genes may result in impaired adipogenesis, potentially leading to larger fat cells in subcutaneous adipose tissue and insulin resistance. ..
- Ikezoe T, Gery S, Yin D, O Kelly J, Binderup L, Lemp N, et al. CCAAT/enhancer-binding protein delta: a molecular target of 1,25-dihydroxyvitamin D3 in androgen-responsive prostate cancer LNCaP cells. Cancer Res. 2005;65:4762-8 pubmed..Taken together, forced expression of C/EBPdelta in cancer cells may be a promising therapeutic strategy. ..
- Unoki M, Brunet J, Mousli M. Drug discovery targeting epigenetic codes: the great potential of UHRF1, which links DNA methylation and histone modifications, as a drug target in cancers and toxoplasmosis. Biochem Pharmacol. 2009;78:1279-88 pubmed publisher..In this review, we discuss several possible methods that can inhibit the multiple unique functions of UHRF1, which can be utilized for treating cancers and toxoplasmosis. ..
- Couetil L, Art T, de Moffarts B, Becker M, Mélotte D, Jaspar F, et al. DNA binding activity of transcription factors in bronchial cells of horses with recurrent airway obstruction. Vet Immunol Immunopathol. 2006;113:11-20 pubmed..These data support the view that AP-1 and CREB play a role in modulating airway inflammation in horses with RAO. ..
- Missiou A, Wolf D, Platzer I, Ernst S, Walter C, Rudolf P, et al. CD40L induces inflammation and adipogenesis in adipose cells--a potential link between metabolic and cardiovascular disease. Thromb Haemost. 2010;103:788-96 pubmed publisher..Our data reveal potent metabolic functions of CD40L aside from its known pivotal pro-inflammatory role within plaques. Our data suggest that CD40L may mediate risk at the interface of metabolic and atherothrombotic disease. ..
- Fu Y, Luo N, Klein R, Garvey W. Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. J Lipid Res. 2005;46:1369-79 pubmed
- Becker H, Marcucci G, Maharry K, Radmacher M, Mrozek K, Margeson D, et al. Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated gene- and microRNA-expression signatures: a Cancer and Leukemia Group B study. J Clin Oncol. 2010;28:596-604 pubmed publisher..The gene- and microRNA-expression profiles suggest that NPM1 mutations constitute a marker defining a biologically homogeneous entity in CN-AML that might be treated with specific and/or targeted therapies across age groups. ..
- Chen S, Liu X, Yue P, Schonthal A, Khuri F, Sun S. CCAAT/enhancer binding protein homologous protein-dependent death receptor 5 induction and ubiquitin/proteasome-mediated cellular FLICE-inhibitory protein down-regulation contribute to enhancement of tumor necrosis factor-related apoptosis-inducing l. Mol Pharmacol. 2007;72:1269-79 pubmed..Together, we conclude that DMC sensitizes human NSCLC cells to TRAIL-induced apoptosis via induction of DR5 and down-regulation of c-FLIP. ..
- Roth M, Black J. An imbalance in C/EBPs and increased mitochondrial activity in asthmatic airway smooth muscle cells: novel targets in asthma therapy?. Br J Pharmacol. 2009;157:334-41 pubmed publisher..However, these findings may present the basis for the development of novel curative asthma drugs. ..
- Hsu C, Lu C, Huang B, Wu M, Tsai S. Cyclic adenosine 3',5'-monophosphate response element-binding protein and CCAAT/enhancer-binding protein mediate prostaglandin E2-induced steroidogenic acute regulatory protein expression in endometriotic stromal cells. Am J Pathol. 2008;173:433-41 pubmed publisher..Taken together, PGE(2)-induced StAR promoter activity appears to be regulated by CREB and C/EBPbeta in a cooperative manner in ectopic human endometriotic stromal cells, providing a molecular framework for the etiology of endometriosis. ..
- Unoki M, Bronner C, Mousli M. A concern regarding the current confusion with the human homolog of mouse Np95, ICBP90/UHRF1. Radiat Res. 2008;169:240-4 pubmed publisher..Here we show the revised ICBP90 gene structure and 366 polymorphisms in this gene. Our conclusion is that the human homolog of Np95 is ICBP90, whose gene symbol is UHRF1. ..
- O Kane C, Boyle J, Horncastle D, Elkington P, Friedland J. Monocyte-dependent fibroblast CXCL8 secretion occurs in tuberculosis and limits survival of mycobacteria within macrophages. J Immunol. 2007;178:3767-76 pubmed..These data show that fibroblasts have a previously unrecognized role in modulating inflammation in TB by their CXCL8-dependent contribution to cell recruitment and mycobacterial killing within the granuloma. ..
- Nakanishi K, Sudo T, Morishima N. Endoplasmic reticulum stress signaling transmitted by ATF6 mediates apoptosis during muscle development. J Cell Biol. 2005;169:555-60 pubmed..CHOP was also transiently induced. These results suggest that specific ER stress signaling transmitted by ATF6 leads to naturally occurring apoptosis during muscle development. ..
- Lai W, Wong N. ROS mediates 4HPR-induced posttranscriptional expression of the Gadd153 gene. Free Radic Biol Med. 2005;38:1585-93 pubmed..Our data provide the first evidence that the posttranscriptional expression of the Gadd153 gene can be regulated by ROS produced by 4HPR. ..
- Qiu X, Aiken K, Chokas A, Beachy D, Nick H. Distinct functions of CCAAT enhancer-binding protein isoforms in the regulation of manganese superoxide dismutase during interleukin-1beta stimulation. J Biol Chem. 2008;283:25774-85 pubmed publisher..Our data demonstrating the physiological relevance of the N-terminal peptide also provide a rationale for revisiting the role of LAP* in the regulation of other genes and in pathways such as lipogenesis and development. ..
- Suzuki M, Wang H, McCarty D. Repression of the LEAFY COTYLEDON 1/B3 regulatory network in plant embryo development by VP1/ABSCISIC ACID INSENSITIVE 3-LIKE B3 genes. Plant Physiol. 2007;143:902-11 pubmed..We suggest that VAL targets Sph/RY-containing genes in the network for chromatin-mediated repression in conjunction with the PKL-related CHD3 chromatin-remodeling factors. ..
- Lu G, Leung C, Yan B, Tan C, Low S, Aung M, et al. C/EBPalpha is up-regulated in a subset of hepatocellular carcinomas and plays a role in cell growth and proliferation. Gastroenterology. 2010;139:632-43, 643.e1-4 pubmed publisher..C/EBPalpha is up-regulated in a subset of HCCs and has growth-promoting activities in HCC cells. Novel oncogenic mechanisms involving C/EBPalpha may be amenable to epigenetic regulation to improve treatment outcomes. ..
- Heckman C, Duan H, Garcia P, Boxer L. Oct transcription factors mediate t(14;18) lymphoma cell survival by directly regulating bcl-2 expression. Oncogene. 2006;25:888-98 pubmed..Oct-2, therefore, acts as a cell survival factor in t(14;18) lymphoma cells by directly activating the antiapoptotic gene bcl-2. ..
- Medin C, Fitzgerald K, Rothman A. Dengue virus nonstructural protein NS5 induces interleukin-8 transcription and secretion. J Virol. 2005;79:11053-61 pubmed publisher..Recruitment and activation of potential target cells to sites of DEN2V replication by virus-induced chemokine production may contribute to viral replication as well as to the inflammatory components of dengue virus disease...
- Theilgaard Monch K, Jacobsen L, Rasmussen T, Niemann C, Udby L, Borup R, et al. Highly glycosylated alpha1-acid glycoprotein is synthesized in myelocytes, stored in secondary granules, and released by activated neutrophils. J Leukoc Biol. 2005;78:462-70 pubmed..Hence, neutrophils, which constitute the first line of defense, are likely to serve as the primary local source of AGP at sites of infection or injury. ..
- Li J, Lee D, Cheung B, Lau A. Mechanisms for HIV Tat upregulation of IL-10 and other cytokine expression: kinase signaling and PKR-mediated immune response. FEBS Lett. 2005;579:3055-62 pubmed..We next identified that the MAP kinases including ERK-1/2 and p38 are downstream of PKR in these Tat-induced pathways. Thus, PKR may play a critical role in mediating the subversive effects of HIV Tat resulting in IL-10 induction. ..
- Borger P, Matsumoto H, Boustany S, Gencay M, Burgess J, King G, et al. Disease-specific expression and regulation of CCAAT/enhancer-binding proteins in asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2007;119:98-105 pubmed..Budesonide and formoterol modulate C/EBP expression in a drug- and disease-specific pattern. The data could provide a method to discriminate between asthma and COPD at an early disease stage. ..
- Qiu W, Hu Y, Andersen T, Jafari A, Li N, Chen W, et al. Tumor necrosis factor receptor superfamily member 19 (TNFRSF19) regulates differentiation fate of human mesenchymal (stromal) stem cells through canonical Wnt signaling and C/EBP. J Biol Chem. 2010;285:14438-49 pubmed publisher..In conclusion, we revealed a novel function of TNFRSF19 as a factor mediating differentiation signals that determine the hMSC differentiating fate into osteoblasts or adipocytes. ..
- Papantonis A, Vanden Broeck J, Lecanidou R. Architectural factor HMGA induces promoter bending and recruits C/EBP and GATA during silkmoth chorion gene regulation. Biochem J. 2008;416:85-97 pubmed publisher..A revised model for chorion gene regulation is discussed in view of these findings...
- Samuel W, Kutty R, Vijayasarathy C, Pascual I, Duncan T, Redmond T. Decreased expression of insulin-like growth factor binding protein-5 during N-(4-hydroxyphenyl)retinamide-induced neuronal differentiation of ARPE-19 human retinal pigment epithelial cells: regulation by CCAAT/enhancer-binding protein. J Cell Physiol. 2010;224:827-36 pubmed publisher..Thus, our results clearly demonstrate that the IGFBP5 expression is down-regulated during 4HPR-induced neuronal differentiation of human RPE cells through a MAPK signal transduction pathway involving C/EBPbeta. ..
- Burda P, Curik N, Kokavec J, Basova P, Mikulenkova D, Skoultchi A, et al. PU.1 activation relieves GATA-1-mediated repression of Cebpa and Cbfb during leukemia differentiation. Mol Cancer Res. 2009;7:1693-703 pubmed publisher..Collectively, we show that either activation of PU.1 or inhibition of GATA-1 efficiently reverses the transcriptional block imposed by GATA-1 and leads to the activation of a myeloid transcriptional program directed by PU.1. ..
- Mukhopadhyay P, Ali M, Nandi A, Carreon P, Choy H, Saha D. The cyclin-dependent kinase 2 inhibitor down-regulates interleukin-1beta-mediated induction of cyclooxygenase-2 expression in human lung carcinoma cells. Cancer Res. 2006;66:1758-66 pubmed..Taken together, the data suggest that CDK2 activity may play an important event in the IL-1beta-induced COX-2 expression and prostaglandin E(2) synthesis and might represent a novel target for BMS-387032. ..
- Salma N, Xiao H, Imbalzano A. Temporal recruitment of CCAAT/enhancer-binding proteins to early and late adipogenic promoters in vivo. J Mol Endocrinol. 2006;36:139-51 pubmed..We have concluded that C/EBP family members bind to adipogenic genes in vivo in a manner that follows the induction of C/EBP protein synthesis. ..
- Papaemmanuil E, Hosking F, Vijayakrishnan J, Price A, Olver B, Sheridan E, et al. Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia. Nat Genet. 2009;41:1006-10 pubmed publisher..Notably, all three risk variants map to genes involved in transcriptional regulation and differentiation of B-cell progenitors. ..
- Matak P, Chaston T, Chung B, Srai S, McKie A, Sharp P. Activated macrophages induce hepcidin expression in HuH7 hepatoma cells. Haematologica. 2009;94:773-80 pubmed publisher..Our data suggest that the interleukin-1beta and bone morphogenetic protein signaling pathways are central to the regulation of HAMP expression by macrophages in this co-culture model. ..
- Sari F, Watanabe K, Widyantoro B, Thandavarayan R, Harima M, Zhang S, et al. Partial inactivation of cardiac 14-3-3 protein in vivo elicits endoplasmic reticulum stress (ERS) and activates ERS-initiated apoptosis in ERS-induced mice. Cell Physiol Biochem. 2010;26:167-78 pubmed publisher..The enhancement of 14-3-3 protein may provide a novel protective therapy against cardiac ERS and ERS-initiated apoptosis, at least in part, through the regulation of CHOP and caspase-12 via the Ire1alpha/TRAF2 pathway. ..