Search results for: Roland Schüle

Items from 1 to 20 out of 29 results

article

Next‐generation sequencing reveals a novel role of lysine‐specific demethylase 1 in adhesion of rhabdomyosarcoma cells

Tinka Haydn, Sarah Kehr, Dominica Willmann, Eric Metzger, more

International Journal of Cancer > 146 > 12 > 3435 - 3449

Lysine‐specific demethylase 1 (LSD1), a histone lysine demethylase with the main specificity for H3K4me2, has been shown to be overexpressed in rhabdomyosarcoma (RMS) tumor samples. However, its role in RMS biology is not yet well understood. Here, we identified a new role of LSD1 in regulating adhesion of RMS cells. Genetic knockdown of LSD1 profoundly suppressed clonogenic growth in a panel of RMS...

article

RORβ Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure a Fluid Walking Gait

Stephanie C. Koch, Marta Garcia Del Barrio, Antoine Dalet, Graziana Gatto, more

Neuron > 2017 > 96 > 6 > 1419-1431.e5

Animals depend on sensory feedback from mechanosensory afferents for the dynamic control of movement. This sensory feedback needs to be selectively modulated in a task- and context-dependent manner. Here, we show that inhibitory interneurons (INs) expressing the RORβ orphan nuclear receptor gate sensory feedback to the spinal motor system during walking and are required for the production of a fluid...

article

Lsd1 inhibition induces differentiation and decreases leukemic stem cell frequency in Hoxa9/Meis1-driven AML

Jessica Barth, Anna-Maria Scheder, Sebastian Mohr, Johannes Schulz-Fincke, more

Experimental Hematology > 2017 > 53 > S > S125

article

LSD1 Controls Timely MyoD Expression via MyoD Core Enhancer Transcription

Isabella Scionti, Shinichiro Hayashi, Sandrine Mouradian, Emmanuelle Girard, more

Cell Reports > 2017 > 18 > 8 > 1996-2006

MyoD is a master regulator of myogenesis. Chromatin modifications required to trigger MyoD expression are still poorly described. Here, we demonstrate that the histone demethylase LSD1/KDM1a is recruited on the MyoD core enhancer upon muscle differentiation. Depletion of Lsd1 in myoblasts precludes the removal of H3K9 methylation and the recruitment of RNA polymerase II on the core enhancer, thereby...

article

Overexpression of histone demethylase Fbxl10 leads to enhanced migration in mouse embryonic fibroblasts

Magdalena Rohde, Elisabeth Sievers, Andreas Janzer, Dominica Willmann, more

Experimental Cell Research > 2016 > 348 > 2 > 123-131

Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing, immune responses and invasive tumors all require the orchestrated movement of cells to specific locations.Histone demethylase proteins alter transcription by regulating the chromatin state at specific gene loci. FBXL10 is a conserved and ubiquitously...

article

Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue

Delphine Duteil, Milica Tosic, Franziska Lausecker, Hatice Z. Nenseth, more

Cell Reports > 2016 > 17 > 4 > 1008-1021

Previous work indicated that lysine-specific demethylase 1 (Lsd1) can positively regulate the oxidative and thermogenic capacities of white and beige adipocytes. Here we investigate the role of Lsd1 in brown adipose tissue (BAT) and find that BAT-selective Lsd1 ablation induces a shift from oxidative to glycolytic metabolism. This shift is associated with downregulation of BAT-specific and upregulation...

article

Preparation data of the bromodomains BRD3(1), BRD3(2), BRD4(1), and BRPF1B and crystallization of BRD4(1)-inhibitor complexes

Martin Hügle, Xavier Lucas, Gerhard Weitzel, Dmytro Ostrovskyi, more

Data in Brief > 2016 > 7 > C > 1370-1374

This article presents detailed purification procedures for the bromodomains BRD3(1), BRD3(2), BRD4(1), and BRPF1B. In addition we provide crystallization protocols for apo BRD4(1) and BRD4(1) in complex with numerous inhibitors. The protocols described here were successfully applied to obtain affinity data by isothermal titration calorimetry (ITC) and by differential scanning fluorimetry (DSF) as...

article

SNAIL1 combines competitive displacement of ASCL2 and epigenetic mechanisms to rapidly silence the EPHB3 tumor suppressor in colorectal cancer

Kerstin Rönsch, Sabine Jägle, Katja Rose, Maximilian Seidl, more

Molecular Oncology > 2015 > 9 > 2 > 335-354

EPHB3 is a critical cellular guidance factor in the intestinal epithelium and an important tumor suppressor in colorectal cancer (CRC) whose expression is frequently lost at the adenoma-carcinoma transition when tumor cells become invasive. The molecular mechanisms underlying EPHB3 silencing are incompletely understood. Here we show that EPHB3 expression is anti-correlated with inducers of epithelial-mesenchymal...

article

Tumoral expression of nuclear cofactor FHL2 is associated with lymphatic metastasis in sporadic but not in HNPCC-associated colorectal cancer

Lukman Al-Nomani, Jacqueline Friedrichs, Roland Schüle, Reinhard Büttner, more

Pathology - Research and Practice > 2015 > 211 > 2 > 171-174

Four and a half LIM domain protein-2 (FHL2) is part of the focal adhesion structures modulating cell motility. FHL2 may translocate into the nucleus serving as a transcriptional cofactor binding several transcription factors. Overexpression of FHL2 has been linked to cancer progression in various neoplasias. The aim of the present study was to determine, whether FHL2's function as nuclear cofactor...

article

TGF-β1-dependent induction and nuclear translocation of FHL2 promotes keratin expression in pilomatricoma

Jacqueline Friedrichs, Dennis Fink, Cornelia Mauch, Dagmar Kindler, more

Virchows Archiv > 2015 > 466 > 2 > 199-208

Pilomatricoma is a tumour derived from hair matrix cells, which shows progressive keratin expression. Tumorigenesis is frequently associated with activating mutations in β-catenin gene inducing nuclear expression of β-catenin protein. The present study analysed the role of transforming growth factor-β1 (TGF-β1) and four-and-a-half LIM domain protein 2 (FHL2) in pilomatricoma in synopsis with their...

article

Lysine-Specific Demethylase 1 Has Dual Functions as a Major Regulator of Androgen Receptor Transcriptional Activity

Changmeng Cai, Housheng Hansen He, Shuai Gao, Sen Chen, more

Cell Reports > 2014 > 9 > 5 > 1618-1627

Lysine-Specific Demethylase 1 (LSD1, KDM1A) functions as a transcriptional corepressor through demethylation of histone 3 lysine 4 (H3K4) but has a coactivator function on some genes through mechanisms that are unclear. We show that LSD1, interacting with CoREST, associates with and coactivates androgen receptor (AR) on a large fraction of androgen-stimulated genes. A subset of these AR/LSD1-associated...

article

4‐Acyl Pyrroles: Mimicking Acetylated Lysines in Histone Code Reading

Xavier Lucas, Daniel Wohlwend, Martin Hügle, Karin Schmidtkunz, more

Angewandte Chemie > 125 > 52 > 14305 - 14309

Bromodomänen sind Proteine, die epigenetische Acetyllysin‐Modifizierungen erkennen. Niedermolekulare Inhibitoren, die dort angreifen, könnten entzündungshemmend, antiviral und gegen Krebs aktiv sein. Ein 4‐Acylpyrrol‐Derivat (gelbes Stabmodell in der Erkennungstasche) wurde identifiziert, das spezifische Bromodomänen hemmt und antiproliferativ auf Leukämie‐Zelllinien wirkt.

article

4‐Acyl Pyrroles: Mimicking Acetylated Lysines in Histone Code Reading

Xavier Lucas, Daniel Wohlwend, Martin Hügle, Karin Schmidtkunz, more

Angewandte Chemie International Edition > 52 > 52 > 14055 - 14059

Bromodomains are acetyllysine epigenetic mark reader proteins. Small molecules inhibiting them have potential as anti‐inflammatory, antiviral, and anticancer agents. A 4‐acyl pyrrole derivative (see yellow structure in recognition pocket) has been identified that potently inhibits specific bromodomains and exhibits antiproliferative activity against leukemia cell lines.

article

Impairment of prostate cancer cell growth by a selective and reversible lysine‐specific demethylase 1 inhibitor

Dominica Willmann, Soyoung Lim, Stefan Wetzel, Eric Metzger, more

International Journal of Cancer > 131 > 11 > 2704 - 2709

Post‐translational modifications of histones by chromatin modifying enzymes regulate chromatin structure and gene expression. As deregulation of histone modifications contributes to cancer progression, inhibition of chromatin modifying enzymes such as histone demethylases is an attractive therapeutic strategy to impair cancer growth. Lysine‐specific demethylase 1 (LSD1) removes mono‐ and dimethyl...

article

Targeting of syndecan‐1 by microRNA miR‐10b promotes breast cancer cell motility and invasiveness via a Rho‐GTPase‐ and E‐cadherin‐dependent mechanism

Sherif A. Ibrahim, George W. Yip, Christian Stock, Jun‐Wei Pan, more

International Journal of Cancer > 131 > 6 > E884 - E896

microRNAs are small endogenous noncoding RNAs, which post‐transcriptionally regulate gene expression. In breast cancer, overexpression of the transmembrane heparan sulfate proteoglycan syndecan‐1, a predicted target of the oncomiR miR‐10b, correlates with poor clinical outcome. To investigate the potential functional relationship of miR‐10b and syndecan‐1, MDA‐MB‐231 and MCF‐7 breast cancer cells...

article

Four-and-a-half LIM domains protein 2 (FHL2) is associated with the development of craniofacial musculature in the teleost fish Sparus aurata

Marta S. Rafael, Vincent Laizé, Anabela Bensimon-Brito, Ricardo B. Leite, more

Cellular and Molecular Life Sciences > 2012 > 69 > 3 > 423-434

Four-and-a-half LIM domains protein 2 (FHL2) is involved in major cellular mechanisms such as regulation of gene transcription and cytoskeleton modulation, participating in physiological control of cardiogenesis and osteogenesis. Knowledge on underlying mechanisms is, however, limited. We present here new data on FHL2 protein and its role during vertebrate development using a marine teleost fish,...

article

Lysine-specific demethylase 1 is highly expressed in solitary fibrous tumors, synovial sarcomas, rhabdomyosarcomas, desmoplastic small round cell tumors, and malignant peripheral nerve sheath tumors

Hans-Ulrich Schildhaus, Raffael Riegel, Wolfgang Hartmann, Susanne Steiner, more

Human Pathology > 2011 > 42 > 11 > 1667-1675

Epigenetic changes including histone methylation, histone acetylation, and DNA methylation are thought to play important roles in the onset and progression of cancer in numerous tumor types. Recent evidence shows that dysregulated epigenetic modifications are as significant as genetic mutations and can act as oncogenic driver lesions causing autonomous growth of cancer cells. Here, we investigated...

article

Acyl derivatives of p-aminosulfonamides and dapsone as new inhibitors of the arginine methyltransferase hPRMT1

Elisabeth-Maria Bissinger, Ralf Heinke, Astrid Spannhoff, Adrien Eberlin, more

Bioorganic & Medicinal Chemistry > 2011 > 19 > 12 > 3717-3731

Arginine methylation is an epigenetic modification that receives increasing interest as it plays an important role in several diseases. This is especially true for hormone-dependent cancer, seeing that histone methylation by arginine methyltransferase I (PRMT1) is involved in the activation of sexual hormone receptors. Therefore, PRMT inhibitors are potential drugs and interesting tools for cell biology...

article

Epigenetic regulation of cancer growth by histone demethylases

Soyoung Lim, Eric Metzger, Roland Schüle, Jutta Kirfel, more

International Journal of Cancer > 127 > 9 > 1991 - 1998

Cancer is traditionally viewed as a primarily genetic disorder. However, it is now increasingly apparent that epigenetic abnormalities play a fundamental role in cancer development. Aberrant expression of histone‐modifying enzymes has been implicated in the course of tumor initiation and progression. The discovery of a large number of histone demethylases suggests an important role for dynamic regulation...

article

Alterations in excitotoxicity and prostaglandin metabolism in a transgenic mouse model of Alzheimer's disease

Eva C. Schulte, Helen Slawik, Roland Schüle, Thomas Gunther, more

Neurochemistry International > 2009 > 55 > 7 > 689-696

To address the potential impact of presenilin mutations on the prostaglandin metabolism in a neurodegenerative model of glutamatergic excitotoxicity, we injected kainic acid intraperitoneally (30mg/kg body weight) into mice over-expressing the human N141I mutation of presenilin-2, which is known to cause an early-onset form of Alzheimer's disease. We compared the seizure activity as well as seizure...

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INFONA - science communication portal

Search results for: Roland Schüle

Next‐generation sequencing reveals a novel role of lysine‐specific demethylase 1 in adhesion of rhabdomyosarcoma cells

RORβ Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure a Fluid Walking Gait

Lsd1 inhibition induces differentiation and decreases leukemic stem cell frequency in Hoxa9/Meis1-driven AML

LSD1 Controls Timely MyoD Expression via MyoD Core Enhancer Transcription

Overexpression of histone demethylase Fbxl10 leads to enhanced migration in mouse embryonic fibroblasts

Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue

Preparation data of the bromodomains BRD3(1), BRD3(2), BRD4(1), and BRPF1B and crystallization of BRD4(1)-inhibitor complexes

SNAIL1 combines competitive displacement of ASCL2 and epigenetic mechanisms to rapidly silence the EPHB3 tumor suppressor in colorectal cancer

Tumoral expression of nuclear cofactor FHL2 is associated with lymphatic metastasis in sporadic but not in HNPCC-associated colorectal cancer

TGF-β1-dependent induction and nuclear translocation of FHL2 promotes keratin expression in pilomatricoma

Lysine-Specific Demethylase 1 Has Dual Functions as a Major Regulator of Androgen Receptor Transcriptional Activity

4‐Acyl Pyrroles: Mimicking Acetylated Lysines in Histone Code Reading

4‐Acyl Pyrroles: Mimicking Acetylated Lysines in Histone Code Reading

Impairment of prostate cancer cell growth by a selective and reversible lysine‐specific demethylase 1 inhibitor

Targeting of syndecan‐1 by microRNA miR‐10b promotes breast cancer cell motility and invasiveness via a Rho‐GTPase‐ and E‐cadherin‐dependent mechanism

Four-and-a-half LIM domains protein 2 (FHL2) is associated with the development of craniofacial musculature in the teleost fish Sparus aurata

Lysine-specific demethylase 1 is highly expressed in solitary fibrous tumors, synovial sarcomas, rhabdomyosarcomas, desmoplastic small round cell tumors, and malignant peripheral nerve sheath tumors

Acyl derivatives of p-aminosulfonamides and dapsone as new inhibitors of the arginine methyltransferase hPRMT1

Epigenetic regulation of cancer growth by histone demethylases

Alterations in excitotoxicity and prostaglandin metabolism in a transgenic mouse model of Alzheimer's disease

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