A5087187459- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Autophagy in Disease and Therapy
- Cancer-related Molecular Pathways
- Wnt/β-catenin signaling in development and cancer
- Glycosylation and Glycoproteins Research
- Cancer Mechanisms and Therapy
- RNA Research and Splicing
- HER2/EGFR in Cancer Research
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Advanced biosensing and bioanalysis techniques
- Kruppel-like factors research
- 14-3-3 protein interactions
- Cellular transport and secretion
- ATP Synthase and ATPases Research
- Lung Cancer Treatments and Mutations
- Peroxisome Proliferator-Activated Receptors
- Peptidase Inhibition and Analysis
- Endoplasmic Reticulum Stress and Disease
- Heat shock proteins research
- RNA and protein synthesis mechanisms
- Acute Myeloid Leukemia Research
Goethe University Frankfurt
2014-2024
University Hospital Frankfurt
2019-2023
Klinikum rechts der Isar
2008-2023
Medical Research Council
2009-2014
MRC Laboratory of Molecular Biology
2009-2014
München Klinik
2008
Technical University of Munich
2008
In eukaryotic cells the stability and function of many proteins are regulated by addition ubiquitin or ubiquitin-like peptides. This process is dependent upon sequential action an E1-activating enzyme, E2-conjugating E3 ligase. Different combinations these confer substrate specificity form protein modification. However, combinatorial preferences within ubiquitination networks remain unclear. this study, yeast two-hybrid (Y2H) screens were combined with true homology modeling methods to...
Abstract Hypoxia induces massive changes in alternative splicing (AS) to adapt cells the lack of oxygen. Here, we identify factor SRSF6 as a key AS response hypoxia. The level is strongly reduced acute hypoxia, which serves dual purpose: it allows for exon skipping and triggers dispersal nuclear speckles. Our data suggest that use speckles reprogram their gene expression during hypoxic adaptation plays an important role cohesion Down-regulation achieved through inclusion poison cassette...
Abstract The transcription factor HIF‐1α is essential for cells to rapidly adapt low oxygen levels (hypoxia). frequently deregulated in cancer and correlates with poor patient prognosis. Here, we demonstrate that the deubiquitinase Cezanne regulates homeostasis. Loss of decreases target gene expression due a reduction protein levels. Surprisingly, although Cezanne‐regulated degradation depends on tumour suppressor pVHL , hydroxylase proteasome activity are dispensable. Our data suggest...
Abstract Mutations of the tumor suppressor E-cadherin and overexpression receptor tyrosine kinase epidermal growth factor (EGFR) are among most frequent genetic alterations associated with diffuse-type gastric carcinoma. Accumulating evidence suggests a functional relationship between EGFR that regulates both proteins. We report somatic mutation is increased activation followed by enhanced recruitment downstream acting signaling components binding protein 2 Shc, Ras. Reduced complex...
Mechanisms regulating protein degradation ensure the correct and timely expression of transcription factors such as hypoxia inducible factor (HIF). Under normal oxygen tensions, HIFα subunits are targeted for proteasomal mainly by vHL-dependent ubiquitination. Deubiquitinases responsible reversing this process. While mechanism regulation ubiquitin-dependent has been object many studies, little is known about role deubiquitinases. Here we show that HIF2α regulated deubiquitinase Cezanne in an...
Current technologies used to generate CRISPR/Cas gene perturbation reagents are labor intense and require multiple ligation cloning steps. Furthermore, increasing gRNA sequence diversity negatively affects distribution, leading libraries of heterogeneous quality. Here, we present a rapid cloning-free mutagenesis technology that can efficiently covalently-closed-circular-synthesized (3Cs) uncouples from distribution. We demonstrate the fidelity performance 3Cs by tailored targeting all human...
Deubiquitinases (DUBs) are vital for the regulation of ubiquitin signals, and both catalytic activity target recruitment by DUBs need to be tightly controlled. Here, we identify asparagine hydroxylation as a novel posttranslational modification involved in Cezanne (also known OTU domain-containing protein 7B (OTUD7B)), DUB that controls key cellular functions signaling pathways. We demonstrate is substrate factor inhibiting HIF1 (FIH1)- oxygen-dependent hydroxylation. found FIH1 modifies...
Autophagy is a major cellular quality control system responsible for the degradation of proteins and organelles in response to stress damage maintain homeostasis. Ubiquitination autophagy-related or regulatory components important precise autophagy pathways. Here, we show that deubiquitinase ubiquitin-specific protease 11 (USP11) restricts KO USP11 mammalian cells results elevated autophagic flux. We also demonstrate depletion homolog H34C03.2 Caenorhabditis elegans triggers hyperactivation...
The nucleolar scaffold protein NPM1 is a multifunctional regulator of cellular homeostasis, genome integrity, and stress response. mutations, known as NPM1c variants promoting its aberrant cytoplasmic localization, are the most frequent genetic alterations in acute myeloid leukemia (AML). A hallmark AML cells their dependency on elevated autophagic flux. Here, we show that induce autophagy-lysosome pathway by activating master transcription factor TFEB, thereby coordinating expression...
<div>Abstract<p>Mutations of the tumor suppressor E-cadherin and overexpression receptor tyrosine kinase epidermal growth factor (EGFR) are among most frequent genetic alterations associated with diffuse-type gastric carcinoma. Accumulating evidence suggests a functional relationship between EGFR that regulates both proteins. We report somatic mutation is increased activation followed by enhanced recruitment downstream acting signaling components binding protein 2 Shc, Ras....
Supplementary Results, Figure 1, Methods and Materials from Enhanced Activation of Epidermal Growth Factor Receptor Caused by Tumor-Derived E-Cadherin Mutations