A5011132701- Cellular Mechanics and Interactions
- RNA Research and Splicing
- Cell Adhesion Molecules Research
- Protein Kinase Regulation and GTPase Signaling
- Chronic Myeloid Leukemia Treatments
- Cancer Cells and Metastasis
- Signaling Pathways in Disease
- RNA modifications and cancer
- Cytokine Signaling Pathways and Interactions
- Skin and Cellular Biology Research
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Cellular transport and secretion
- Cardiomyopathy and Myosin Studies
- Cardiac Fibrosis and Remodeling
- Cancer-related gene regulation
- Quinazolinone synthesis and applications
- Epigenetics and DNA Methylation
- Melanoma and MAPK Pathways
- Chemical Synthesis and Analysis
- MicroRNA in disease regulation
- Connective Tissue Growth Factor Research
- TGF-β signaling in diseases
- NF-κB Signaling Pathways
- Nuclear Structure and Function
Martin Luther University Halle-Wittenberg
2014-2024
Max Planck Institute of Biochemistry
2006-2017
Wittenberg University
2013
Faculty (United Kingdom)
2013
Luther University
2013
Physiological Society
2013
Max Planck Society
2009-2012
The Honourable Society of Lincoln's Inn
2002-2004
Cancer Research UK
2002-2004
University of Würzburg
1999-2000
The oncofetal mRNA-binding protein IGF2BP1 and the transcriptional regulator SRF modulate gene expression in cancer. In cancer cells, we demonstrate that promotes of a conserved N6-methyladenosine (m6A)-dependent manner by impairing miRNA-directed decay mRNA. This results enhanced SRF-dependent activity tumor cell growth invasion. At post-transcriptional level, sustains various SRF-target genes. majority these SRF/IGF2BP1-enhanced genes, including PDLIM7 FOXK1, show upregulation with...
Signal-induced activation of the transcription factor serum response (SRF) requires alterations in actin dynamics. SRF activity can be inhibited by ectopic expression beta-actin, either because itself participates regulation or as a consequence cytoskeletal perturbations. To distinguish between these possibilities, we studied mutants. Three mutant actins, G13R, R62D, and C-terminal VP16 fusion protein, were shown not to polymerize vivo, judged two-hybrid, immunofluorescence, cell...
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Hepatocyte growth factor (HGF; scatter factor) is a multipotent protein with mitogenic, motogenic, and developmental functions. Upon activation, the HGF-receptor c-Met binds phosphorylates multisite docking Gab1. Besides binding motifs for phosphatidylinositol 3-kinase Grb2, Gab 1 contains multiple Tyr-<i>X</i>-<i>X</i>-Pro (Y<i>XX</i>P) which, when phosphorylated, are potential sites adapter proteins c-Crk Crk-like (CRKL). Stimulation of human embryonic kidney cells (HEK293) HGF leads to...
Epithelial cell-cell junctions are specialised structures connecting individual cells in epithelial tissues. They dynamically and functionally linked to the actin cytoskeleton. Disassembly of these is a key event during physiological pathological processes, but how this influences gene expression largely uncharacterised. Here, we investigate whether junction disassembly regulates transcription by serum response factor (SRF) its coactivator MAL/MRTF. Ca2+-dependent dissociation integrity was...
Monomeric actin regulates gene expression through serum response factor (SRF) by inhibiting its transcriptional coactivator myocardin-related transcription (MAL/MRTF). Many affected genes encode cytoskeletal components. We have analysed the migratory effects of actin–MAL signalling and new target in non-invasive highly adherent cells. Expression active MAL impaired migration both fibroblasts epithelial cells, whereas dominant-negative constructs partial knockdown MAL/MRTF enhanced motility....
Pulmonary arterial hypertension (PAH) is a fatal disease for which no cure yet available. The leading cause of death in PAH right ventricular (RV) failure. Previously, the TNF receptor superfamily member fibroblast growth factor-inducible molecule 14 (Fn14) has been associated with different fibrotic diseases. However, so far there study demonstrating causal role endogenous Fn14 signaling RV or LV heart disease. purpose this was to determine whether global ablation prevents fibrosis and...
ABSTRACT Integrin-mediated activation of small GTPases induces the polymerisation G-actin into various actin structures and release transcriptional co-activator MRTF from G-actin. Here we report that pan-integrin-null fibroblasts seeded on fibronectin expressing β1- and/or αV-class integrin contained different pools, nuclear MRTF-A (also known as MKL1 or MAL) levels MRTF-A–SRF activities. The activities were highest in cells both classes, lower β1 integrins lowest αV integrins. Quantitative...
MAPKs are crucially involved in the regulation of growth and differentiation a variety cells. To elucidate role keratinocyte differentiation, activation ERK, JNK, p38 response to stimulation with extracellular calcium was analyzed. We provide evidence that calcium-induced keratinocytes is associated rapid transient Raf/MEK/ERK pathway. Stimulation resulted Raf isozymes their downstream effector ERK within 10-15 min, but did not increase JNK or activity. Calcium-induced differed kinetics from...
Interferon (IFN) regulatory factors (IRFs) are a family of transcription among which IRF-1, IRF-2, and IFN consensus sequence binding protein (ICSBP). These share homology in the N-terminal DNA-binding domain. IRF-1 IRF-2 further related have additional homologous sequences within their C-termini. Whereas ICSBP identified as transcriptional repressors, is an activator. In present work, identification functional domains murine with regard to DNA-binding, nuclear translocation,...
Neuronal motility relies on actin treadmilling. In addition to regulating cytoskeletal dynamics in the cytoplasm, modulates nuclear gene expression. We present a hitherto unappreciated cross talk of signaling with expression governing neuronal motility. Toward this end, we used novel approach using mutant actins either favoring (G15S) or inhibiting (R62D) F-actin assembly. Overexpressing these mouse hippocampal neurons not only modulated growth-cone function but also neurite elongation,...
Expression of connective tissue growth factor (CTGF) in endothelial cells is modulated by shear stress affecting the organization cytoskeleton. The molecular connection between alterations actin and CTGF expression was investigated human umbilical vein (HUVEC) a microvascular cell line. Overexpression nonpolymerizable monomeric R62D interfered with fiber formation HUVEC concomitantly reduced immunoreactive CTGF. In cells, flow-dependent upregulation prevented this mutant. contrast,...
Abstract Tumour growth and metastatic colonization is strongly influenced by the tumour stroma, including cancer-associated fibroblasts (CAF). Multipotent mesenchymal stromal cells (MSC) are a possible source of CAF following myofibroblastic differentiation, we have previously shown that MSC support growth. Triggered cell-derived factors like transforming factor β1 (TGF-β1), differentiation associated with increased expression markers alpha smooth muscle actin (α-SMA). Here show...
Myocardin-related transcription factors (MRTF) A and B link actin dynamics mechanotransduction to gene expression. In mice, MRTF-A is involved in mammary gland differentiation, but its role human epithelial cells remains unclear.Three-dimensional cultures of MCF10A were used model acinar morphogenesis. Stable knockdown, MRTF-A/B rescue overexpression was established characterize the functional during morphogenesis using confocal microscopy expression analysis. Breast cancer patient databases...