O-GlcNAcylation is involved in the transcriptional activity of EWS-FLI1 in Ewing's sarcoma.


:The oncogene EWS-FLI1 encodes a chimeric transcription factor expressed in Ewing's sarcoma family tumors (ESFTs). EWS-FLI1 target gene expression is thought to drive ESFT pathogenesis and, therefore, inhibition of EWS-FLI1 activity holds high therapeutic promise. As the activity of many transcription factors is regulated by post-translational modifications, we studied the presence of modifications on EWS-FLI1. The immuno-purified fusion-protein was recognized by an antibody specific for O-linked beta-N-acetylglucosaminylation, and bound readily to a phosphoprotein-specific dye. Inhibition of Ser/Thr-specific phophatases increased EWS-FLI1 molecular weight and reduced its O-GlcNAc content, suggesting that phosphorylation and O-GlcNAcylation of EWS-FLI1 interact dynamically. By mutation analysis, O-GlcNAcylation was delineated to Ser/Thr residues of the amino-terminal EWS transcriptional-activation domain. Metabolic inhibition of the hexosamine biosynthetic pathway abrogated O-GlcNAcylation of EWS-FLI1 and interfered specifically with transcriptional activation of the EWS-FLI1 target Id2. These results suggest that drugs modulating glycosylation of EWS-FLI1 interfere functionally with its activity and might, therefore, constitute promising additions to the current ESFT chemotherapy.






Bachmaier R,Aryee DN,Jug G,Kauer M,Kreppel M,Lee KA,Kovar H




Has Abstract


2009-03-05 00:00:00
















  • Snail is a repressor of RKIP transcription in metastatic prostate cancer cells.

    abstract::Diminished expression of the metastasis suppressor protein RKIP was previously reported in a number of cancers. The underlying mechanism remains unknown. Here, we show that the expression of RKIP negatively correlates with that of Snail zinc-transcriptional repressor, a key modulator of normal and neoplastic epithelia...


    pub_type: 杂志文章


    authors: Beach S,Tang H,Park S,Dhillon AS,Keller ET,Kolch W,Yeung KC

    更新日期:2008-04-03 00:00:00

  • The MutSβ complex is a modulator of p53-driven tumorigenesis through its functions in both DNA double-strand break repair and mismatch repair.

    abstract::Loss of the DNA mismatch repair (MMR) protein MSH3 leads to the development of a variety of tumors in mice without significantly affecting survival rates, suggesting a modulating role for the MutSβ (MSH2-MSH3) complex in late-onset tumorigenesis. To better study the role of MSH3 in tumor progression, we crossed Msh3(-...


    pub_type: 杂志文章


    authors: van Oers JM,Edwards Y,Chahwan R,Zhang W,Smith C,Pechuan X,Schaetzlein S,Jin B,Wang Y,Bergman A,Scharff MD,Edelmann W

    更新日期:2014-07-24 00:00:00

  • Identification of candidate target genes for EVI-1, a zinc finger oncoprotein, using a novel selection strategy.

    abstract::We have sought to identify and isolate target genes for the zinc finger protein, EVI-1, which has been implicated in the genesis of myelogenous leukemia both in mouse and human. We have approached this with a two-step selection: we first selected for genomic fragments of mouse DNA that bind to the protein with high af...


    pub_type: 杂志文章


    authors: Kim JH,Hui P,Yue D,Aycock J,Leclerc C,Bjoring AR,Perkins AS

    更新日期:1998-09-24 00:00:00

  • Human p53 binds DNA as a protein homodimer but monomeric variants retain full transcription transactivation activity.

    abstract::Wild-type human p53 protein is able to self-associate and consists predominantly of homotetramers in solution. In earlier work we identified the protein sequence motifs involved in p53 quaternary structure and showed that while monomeric p53 protein retains tumour suppressor function, monomeric tumour mutant p53 lacks...


    pub_type: 杂志文章


    authors: Tarunina M,Jenkins JR

    更新日期:1993-11-01 00:00:00

  • Alanine mutagenesis of conserved residues in the platelet-derived growth factor family: identification of residues necessary for dimerization and transformation.

    abstract::Platelet-derived growth factor (PDGF) and vascular endothelial growth factor define a family of dimeric proteins characterized by eight conserved cysteine residues involved in disulfide bonds. Thirteen non-cysteine residues conserved among the platelet-derived/vascular endothelial growth factors were individually muta...


    pub_type: 杂志文章


    authors: Maher DW,Strawn LM,Donoghue DJ

    更新日期:1993-03-01 00:00:00

  • Stanniocalcin-1 acts in a negative feedback loop in the prosurvival ERK1/2 signaling pathway during oxidative stress.

    abstract::Mammalian Stanniocalcin-1 (STC1) is a glycoprotein that has been implicated in various biological processes including angiogenesis. Aberrant STC1 expression has been reported in breast, ovarian and prostate cancers, but the significance of this is not well understood. Here, we report that oxidative stress caused a 40-...


    pub_type: 杂志文章


    authors: Nguyen A,Chang AC,Reddel RR

    更新日期:2009-05-07 00:00:00

  • A role for mismatch repair in control of DNA ploidy following DNA damage.

    abstract::Many reports have shown a link between mismatch repair (MMR) deficiency and loss of normal cell cycle control, particularly loss of G2 arrest. However almost all of these studies utilized transformed cell lines, and thus the involvement of other genes in this phenotype cannot be excluded. We have examined the effects ...


    pub_type: 杂志文章


    authors: Strathdee G,Sansom OJ,Sim A,Clarke AR,Brown R

    更新日期:2001-04-05 00:00:00

  • Developmental regulation of intermediate filament and actin mRNAs during myogenesis is disrupted by oncogenic ras genes.

    abstract::Terminal differentiation of skeletal myoblasts is accompanied by down-regulation of vimentin and beta-, gamma-actins and up-regulation of desmin and sarcomeric alpha-actin(s). To investigate whether the normal decline in expression of vimentin and beta-, gamma-actins was coupled to withdrawal of proliferating myoblast...


    pub_type: 杂志文章


    authors: Olson EN,Capetanaki YG

    更新日期:1989-07-01 00:00:00

  • Human T-cell leukemia virus type I and adult T-cell leukemia.

    abstract::Human T-cell leukemia virus type I (HTLV-I) causes adult T-cell leukemia (ATL) in about 5% of carriers after a long latent period. After its infection, HTLV-I promotes the clonal proliferation of HTLV-I infected cells in vivo by actions of encoded viral proteins, including Tax. However, leukemic cells frequently lack ...


    pub_type: 杂志文章,评审


    authors: Matsuoka M

    更新日期:2003-08-11 00:00:00

  • FOXA1 inhibits prostate cancer neuroendocrine differentiation.

    abstract::Neuroendocrine prostate cancer (NEPC) has increasingly become a clinical challenge. The mechanisms by which neuroendocrine (NE) cells arises from prostate adenocarcinoma cells are poorly understood. FOXA1 is a transcription factor of the forkhead family that is required for prostate epithelial differentiation. In this...


    pub_type: 杂志文章


    authors: Kim J,Jin H,Zhao JC,Yang YA,Li Y,Yang X,Dong X,Yu J

    更新日期:2017-07-13 00:00:00

  • Synergistic action of Smad4 and Pten in suppressing pancreatic ductal adenocarcinoma formation in mice.

    abstract::Mutations of SMAD4/DPC4 are found in about 60% of human invasive pancreatic ductal adenocarcinomas (PDACs); yet, the manner in which SMAD4 deficiency enhances tumorigenesis remains elusive. Using a Cre-LoxP approach, we generated a mutant mouse carrying a targeted deletion of Smad4 in the pancreas. We showed that the ...


    pub_type: 杂志文章


    authors: Xu X,Ehdaie B,Ohara N,Yoshino T,Deng CX

    更新日期:2010-02-04 00:00:00

  • Current role of antibody therapy in patients with metastatic colorectal cancer.

    abstract::In less than 10 years, the number and importance of non-surgical treatment modalities in patients with colorectal cancer (CRC) have increased dramatically, both in the adjuvant and the advanced settings. However, despite the improvement of cytotoxic therapy in CRC, many patients still develop progressive disease and u...


    pub_type: 杂志文章,评审


    authors: Pfeiffer P,Qvortrup C,Eriksen JG

    更新日期:2007-05-28 00:00:00

  • Caspase 8-dependent sensitization of cancer cells to TRAIL-induced apoptosis following reovirus-infection.

    abstract::TRAIL (TNF-related apoptosis-inducing ligand) induces apoptosis in susceptible cells by binding to death receptors 4 (DR4) and 5 (DR5). TRAIL preferentially induces apoptosis in transformed cells and the identification of mechanisms by which TRAIL-induced apoptosis can be enhanced may lead to novel cancer chemotherape...


    pub_type: 杂志文章


    authors: Clarke P,Meintzer SM,Spalding AC,Johnson GL,Tyler KL

    更新日期:2001-10-18 00:00:00

  • Hepatitis B virus X protein promotes the development of liver fibrosis and hepatoma through downregulation of miR-30e targeting P4HA2 mRNA.

    abstract::Hepatitis B virus (HBV)-induced liver necrosis takes great part in liver cirrhosis progression. However, less is known about whether hepatitis B virus X protein (HBx) has effect on liver fibrosis. Here, we report that HBV leads to liver fibrosis and hepatocarcinogenesis through miR-30e targeting P4HA2. HBV transgenic ...


    pub_type: 杂志文章


    authors: Feng GX,Li J,Yang Z,Zhang SQ,Liu YX,Zhang WY,Ye LH,Zhang XD

    更新日期:2017-12-14 00:00:00

  • RSK2 regulates endocytosis of FGF receptor 1 by phosphorylation on serine 789.

    abstract::FGFR1 (fibroblast growth factor receptor 1) regulates many key cellular responses including proliferation, migration and differentiation through activation of signaling pathways. Irregularities in FGFR1 signaling have been implicated in several pathological conditions, including human cancer. In order to discover nove...


    pub_type: 杂志文章


    authors: Nadratowska-Wesolowska B,Haugsten EM,Zakrzewska M,Jakimowicz P,Zhen Y,Pajdzik D,Wesche J,Wiedlocha A

    更新日期:2014-10-02 00:00:00

  • Medullary thyroid carcinomas in transgenic mice expressing a Polyoma carboxyl-terminal truncated middle-T and wild type small-T antigens.

    abstract::Medullary thyroid carcinoma (MTC) is a rare human tumor affecting the calcitonin-secreting c-cells of the thyroid. Here we report that two independent strains of transgenic mice expressing a Polyomavirus (Py) truncated middle-T antigen (deltaMT), consisting of the amino-terminal 304 amino acids, and the full length Py...


    pub_type: 杂志文章


    authors: Felici A,Giorgio M,Krauzewicz N,Della Rocca C,Santoro M,Rovere P,Manni I,Amati P,Pozzi L

    更新日期:1999-04-08 00:00:00

  • Desmoglein 3 promotes cancer cell migration and invasion by regulating activator protein 1 and protein kinase C-dependent-Ezrin activation.

    abstract::Desmoglein 3 (Dsg3), the pemphigus vulgaris antigen, has recently been shown to be upregulated in squamous cell carcinoma (SCC) and has been identified as a good tumor-specific marker for clinical staging of cervical sentinel lymph nodes in head and neck SCC. However, little is known about its biological function in c...


    pub_type: 杂志文章


    authors: Brown L,Waseem A,Cruz IN,Szary J,Gunic E,Mannan T,Unadkat M,Yang M,Valderrama F,O'Toole EA,Wan H

    更新日期:2014-05-01 00:00:00

  • Overexpression of cyclin D1 in rat fibroblasts causes abnormalities in growth control, cell cycle progression and gene expression.

    abstract::Cyclin D1, a putative G1 cyclin, has been implicated in cell cycle control. The human cyclin D1 gene is located on chromosome 11q13 where DNA rearrangement and amplification have been detected in several types of human cancer. Previous studies demonstrated that the cyclin D1 gene is not only rearranged or amplified bu...


    pub_type: 杂志文章


    authors: Jiang W,Kahn SM,Zhou P,Zhang YJ,Cacace AM,Infante AS,Doi S,Santella RM,Weinstein IB

    更新日期:1993-12-01 00:00:00

  • The Phox2B homeobox gene is mutated in sporadic neuroblastomas.

    abstract::Neuroblastomas are embryonal tumours of the sympatho-adrenal lineage with a clinical course ranging from spontaneous regression to fatal progression. The Phox2B homeobox transcription factor functions in the differentiation of the sympatho-adrenal lineage. Targets of Phox2B are, for example, genes of the (nor)adrenali...


    pub_type: 杂志文章


    authors: van Limpt V,Schramm A,van Lakeman A,Sluis P,Chan A,van Noesel M,Baas F,Caron H,Eggert A,Versteeg R

    更新日期:2004-12-09 00:00:00

  • Lack of class I HLA expression in neuroblastoma is associated with high N-myc expression and hypomethylation due to loss of the MEMO-1 locus.

    abstract::Class I HLA expression is low in neuroblastoma tumours and cell lines. We have recently mapped a modifier of methylation for HLA-C (MEMO-1) to chromosomal bands 1p35-36.1, a region deleted in many neuroblastomas. Hypomethylation of HLA-C is strongly correlated with allelic loss of the MEMO-1 locus. Here, we show that ...


    pub_type: 杂志文章


    authors: Cheng NC,Beitsma M,Chan A,Op den Camp I,Westerveld A,Pronk J,Versteeg R

    更新日期:1996-10-17 00:00:00

  • Functional inactivation of Cdk9 through oligomerization chain reaction.

    abstract::The oligomerization chain reaction (OCR) strategy is a recently described technique for inactivation of target proteins that function as homoassociate complexes. This novel strategy is based on the fusion of self-associating coiled-coil (CC) domain of the nuclear factor promyelocytic leukemia (PML) to target proteins....


    pub_type: 杂志文章


    authors: Napolitano G,Mazzocco A,Fraldi A,Majello B,Lania L

    更新日期:2003-07-31 00:00:00

  • Targeting TYRO3 inhibits epithelial-mesenchymal transition and increases drug sensitivity in colon cancer.

    abstract::Colon cancer is the third leading cause of death from cancer worldwide with less than 10% survival rate at the late stage. Although mutations of certain genes have been implicated in familial colon cancer development, the etiology of the majority of colon cancer remains unknown. Herein, we identified TYRO3 as a potent...


    pub_type: 杂志文章


    authors: Chien CW,Hou PC,Wu HC,Chang YL,Lin SC,Lin SC,Lin BW,Lee JC,Chang YJ,Sun HS,Tsai SJ

    更新日期:2016-11-10 00:00:00

  • Sustained recruitment of phospholipase C-gamma to Gab1 is required for HGF-induced branching tubulogenesis.

    abstract::A distinctive property of Hepatocyte Growth Factor (HGF) is its ability to induce differentiation of tubular structures from epithelial and endothelial cells (branching tubulogenesis). The HGF receptor directly activates PI3 kinase, Ras and STAT signalling pathways and phosphorylates the adaptator GRB2 Associated Bind...


    pub_type: 杂志文章


    authors: Gual P,Giordano S,Williams TA,Rocchi S,Van Obberghen E,Comoglio PM

    更新日期:2000-03-16 00:00:00

  • p21 suppresses inflammation and tumorigenesis on pRB-deficient stratified epithelia.

    abstract::The retinoblastoma gene product (pRb) controls proliferation and differentiation processes in stratified epithelia. Importantly, and in contrast to other tissues, Rb deficiency does not lead to spontaneous skin tumor formation. As the cyclin-dependent kinase inhibitor p21 regulates proliferation and differentiation in...


    pub_type: 杂志文章


    authors: Saiz-Ladera C,Lara MF,Garín M,Ruiz S,Santos M,Lorz C,García-Escudero R,Martínez-Fernández M,Bravo A,Fernández-Capetillo O,Segrelles C,Paramio JM

    更新日期:2014-09-11 00:00:00

  • CHK2-mediated regulation of PARP1 in oxidative DNA damage response.

    abstract::Poly(ADP-ribose) polymerase 1 (PARP1) is a DNA damage sensor, which upon activation, recruits downstream proteins by poly(ADP-ribosyl)ation (PARylation). However, it remains largely unclear how PARP1 activity is regulated. Interestingly, the data obtained through this study revealed that PARP1 was co-immunoprecipitate...


    pub_type: 杂志文章


    authors: Hsu PC,Gopinath RK,Hsueh YA,Shieh SY

    更新日期:2019-02-01 00:00:00

  • Cross-talk between Akt, p53 and Mdm2: possible implications for the regulation of apoptosis.

    abstract::The p53 tumor suppressor protein and the Akt/PKB kinase play important roles in the transduction of pro-apoptotic and anti-apoptotic signals, respectively. We provide evidence that conflicting signals transduced by Akt and p53 are integrated via negative feedback between the two pathways. On the one hand, the combinat...


    pub_type: 杂志文章


    authors: Gottlieb TM,Leal JF,Seger R,Taya Y,Oren M

    更新日期:2002-02-14 00:00:00

  • A new fusion gene NUP98-IQCG identified in an acute T-lymphoid/myeloid leukemia with a t(3;11)(q29q13;p15)del(3)(q29) translocation.

    abstract::NUP98 has been involved in multiple recurrent chromosome rearrangements in leukemia. We identified a novel fusion between NUP98 and IQ motif containing G (IQCG) gene from a de novo acute T-lymphoid/myeloid leukemia harboring t(3;11)(q29q13;p15)del(3)(q29). IQCG has two putative coiled-coil domains and one IQ domain. T...


    pub_type: 杂志文章


    authors: Pan Q,Zhu YJ,Gu BW,Cai X,Bai XT,Yun HY,Zhu J,Chen B,Weng L,Chen Z,Xue YQ,Chen SJ

    更新日期:2008-05-29 00:00:00

  • A kinase-dependent role for EphA2 receptor in promoting tumor growth and metastasis.

    abstract::Receptor tyrosine kinases of the Eph family are upregulated in several different types of cancer. One family member in particular, the EphA2 receptor, has been linked to breast, prostate, lung and colon cancer, as well as melanoma. However, mechanisms by which EphA2 contributes to tumor progression are far from clear....


    pub_type: 杂志文章


    authors: Fang WB,Brantley-Sieders DM,Parker MA,Reith AD,Chen J

    更新日期:2005-11-24 00:00:00

  • Different interactions of Grb2/Ash molecule with the NGF and EGF receptors in rat pheochromocytoma PC12 cells.

    abstract::We have previously shown that nerve growth factor (NGF) induces a rapid and relatively continuous activation of Ras in rat pheochromocytoma PC12 cells while epidermal growth factor (EGF) activates Ras transiently, and that tyrosine kinase activity of the NGF receptor is essential for the activation of Ras (Muroya et a...


    pub_type: 杂志文章


    authors: Hashimoto Y,Matuoka K,Takenawa T,Muroya K,Hattori S,Nakamura S

    更新日期:1994-03-01 00:00:00

  • ZNF185, an actin-cytoskeleton-associated growth inhibitory LIM protein in prostate cancer.

    abstract::We have recently identified ZNF185 as a gene that is downregulated in prostate cancer (PCa), in part via epigenetic alteration, and maybe associated with disease progression. In this study, we cloned the ZNF185 cDNA from normal human prostate tissues and investigated its biological function. We show that ZNF185 is a n...


    pub_type: 杂志文章


    authors: Zhang JS,Gong A,Young CY

    更新日期:2007-01-04 00:00:00