A5031025270- Epigenetics and DNA Methylation
- Lipid Membrane Structure and Behavior
- Toxin Mechanisms and Immunotoxins
- Sphingolipid Metabolism and Signaling
- Kruppel-like factors research
- Glycosylation and Glycoproteins Research
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Transgenic Plants and Applications
- Cancer-related gene regulation
- Peroxisome Proliferator-Activated Receptors
- Cancer, Lipids, and Metabolism
- Tissue Engineering and Regenerative Medicine
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- S100 Proteins and Annexins
- Lysosomal Storage Disorders Research
- Monoclonal and Polyclonal Antibodies Research
- Histone Deacetylase Inhibitors Research
- Microtubule and mitosis dynamics
- Adenosine and Purinergic Signaling
- Galectins and Cancer Biology
- RNA regulation and disease
- Pancreatic function and diabetes
- Cell death mechanisms and regulation
University of Freiburg
2014-2023
University Medical Center Freiburg
2016-2023
University of Alabama at Birmingham
2014
University of Milan
2009
Tissue-specific alternative splicing is critical for the emergence of tissue identity during development, yet role this process in malignant transformation undefined. involves evolutionarily conserved, exons that represent only a minority total identified. Many these conserved have functional features influence signaling pathways to profound biological effect. Here, we determined lineage-specific brain-enriched cassette exon membrane-binding tumor suppressor annexin A7 (ANXA7) diminishes...
Human fibroblasts produce ceramide from sialyllactosylceramide on the plasma membranes. Sialidase Neu3 is known to be membrane associated, while only indirect data suggest association of beta-galactosidase and beta-glucosidase. To determine presence beta-glucosidase membrane, cells were submitted cell surface biotinylation. Biotinylated proteins purified by affinity column analyzed for enzymatic activities artificial substrates. Both enzyme found associated with up-regulated in...
Glioblastoma (GBM) comprises distinct subtypes characterized by their molecular profile. Mesenchymal identity in GBM has been associated with a comparatively unfavorable prognosis, primarily due to inherent resistance of these tumors current therapies. The identification determinants mesenchymal transformation could potentially allow for the discovery new therapeutic targets. Zinc Finger and BTB Domain Containing 18 (ZBTB18/ZNF238/RP58) is zinc finger transcriptional repressor crucial role...
Dysregulation of the NF-κB transcription factor occurs in many cancer types. Krüppel-like family factors (KLFs) regulate expression genes involved cell proliferation, differentiation and survival. Here, we report a new mechanism activation glioblastoma through depletion KLF6 tumor suppressor. We show that transactivates multiple negatively controlling pathway consequently reduces nuclear localization downregulates targets. Reconstitution attenuates their malignant phenotype induces...
// Dieter H. Heiland 1, 2 , Roberto Ferrarese Rainer Claus 3 Fangping Dai Anie P. Masilamani Eva Kling Astrid Weyerbrock Teresia 4 Sven Nelander Maria S. Carro 1 Department of Neurosurgery, Medical Center – University Freiburg, Germany Faculty Medicine, Hematology, Oncology, and Stem Cell Transplantation, Freiburg Center, Immunology, Genetics Pathology Science for Life Laboratories, Uppsala, Sweden Correspondence to: Carro, email: maria.carro@uniklinik-freiburg.de Keywords: Glioblastoma,...
The epidermal growth factor receptor (EGFR) was found to be a valuable target on prostate cancer (PCa) cells. However, EGFR inhibitors mostly failed in clinical studies with patients suffering from PCa. We therefore tested the targeted toxins EGF-PE40 and EGF-PE24mut consisting of natural ligand EGF as binding domain PE40, toxin Pseudomonas Exotoxin A, or PE24mut, de-immunized variant thereof, domains. Both were expressed periplasm E.coli evoked an inhibition protein biosynthesis...
Background: Upregulation of anti-apoptotic Bcl-2 proteins in advanced prostate cancer leads to therapeutic resistance by prevention cell death. New approaches aim target the for restoration apoptosis. Methods: The immunotoxin hD7-1(VL-VH)-PE40 specifically binds specific membrane antigen (PSMA) on cells and inhibits protein biosynthesis. It was tested with respect its effects expression proteins. Combination BAD-like mimetic ABT-737 examined 3D spheroids view tumor growth survival SCID mouse...
Enhanced fatty acid synthesis is a hallmark of tumors, including glioblastoma. SREBF1/2 regulate the expression enzymes involved in and cholesterol synthesis. Yet, little known about precise mechanism regulating SREBP gene Here, we show that novel interaction between co-activator/co-repressor CTBP tumor suppressor ZBTB18 regulates genes. In line with our findings, metabolic assays glucose tracing analysis confirm reduction several phospholipid species upon expression. Our study identifies...
Proteolytic cleavage is an important post-translational mechanism to increase protein variability and functionality. In cancer, this process can be deregulated shut off tumor-suppressive functions. Here, we report that in glioblastoma (GBM), the tumor suppressor ZBTB18 targeted for by intracellular protease calpain. The N-terminal (Nte) cleaved fragment localizes cytoplasm thus, unable exert gene expression repressive function of uncleaved protein. Mass spectrometry (MS) analysis indicates...
Immunotoxins consist of an antibody or fragment that binds to a specific cell surface structure and cytotoxic domain kills the after cytosolic uptake. Pseudomonas Exotoxin A (PE) based immunotoxins directed against variety tumor entities have successfully entered clinic. PE possesses KDEL-like motif (REDLK) enables toxin travel from sorting endosomes via KDEL-receptor pathway endoplasmic reticulum (ER), where it is transported into cytosol. There, ADP-ribosylates eukaryotic elongation factor...
Background/Aim: Reports on over-expression of the epidermal growth factor receptor (EGFR) in bladder cancer and its function tumorigenesis have suggested to target this antigen. Materials Methods: We generated targeted toxin EGF-PE40 consisting human (EGF) as binding domain PE40, a truncated version Pseudomonas Exotoxin A, domain. was tested EGFR-expressing cells view via flow cytometry, cytotoxicity WST viability assay. Induction apoptosis examined by western blot. Results: The specifically...
The Zing Finger And BTB Domain Containing 18 (ZBTB18; formerly ZNF238) is a transcriptional repressor with crucial role in brain development and neuronal differentiation. We recently showed that ZBTB18 represses poor prognosis-associated genes it primarily silenced mesenchymal GBMs through promoter methylation. To further elucidate the mechanism of function, we performed Mass Spectrometry (MS) analysis co-precipitated proteins SNB19 cells upon overexpression. Our data revealed corepressors...
Abstract Enhanced fatty acid synthesis is a hallmark of tumors, including glioblastoma. SREBF1/2 regulate the expression enzymes involved in and cholesterol synthesis. Yet, little known about precise mechanism regulating SREBP gene Here, we show that novel interaction between co-activator/co-repressor CTBP tumor suppressor ZBTB18 regulates genes. Our study points at CTBP1/2 LSD1 as co-activators genes whose complex functional activity altered by ZBTB18. binding to promoters associated with...
Tissue-specific alternative splicing is critical to the emergence of tissue identity during development, yet its role in malignant transformation undefined. involves evolutionarily-conserved, exons, which represent only a minority total exons. Many, however, have functional features that influence signaling pathways profound biological effect. In brain, Annexin A7 isoform 1 (ANXA7-I1) exclusively expressed mature neurons, while 2 (ANXA7-I2) exon 6 skipped, glial and progenitor cells. We show...
BACKGROUND: Tissue-specific alternative splicing is known to be critical emergence of tissue identity during development, yet its role in malignant transformation undefined. involves evolutionary-conserved, exons, which represent only a minority total exons. Many, however, have functional features that influence activity signaling pathways profound biological effect. Given tissue-specific has determinative brain development and the enrichment genes containing exons for proteins with roles it...
<p>ZBTB18 promoter methylation analysis.</p>
<p>Supplementary Figure legends and tables.</p>
<p>GSEA analysis in BTSC233.</p>
<p>ZBTB18 promoter methylation analysis.</p>
<p>Proliferation, migration and invasion assays in SNB19 cells.</p>
<p>Characterization of ZBTB18 short band by MS.</p>
<p>GSEA analysis in JX6.</p>
<p>Proliferation, migration and invasion assays in BTSC233 JX6 cells.</p>
<p>ZBTB18 promoter methylation analysis.</p>