A5049942833- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Acute Myeloid Leukemia Research
- Peptidase Inhibition and Analysis
- Cancer-related Molecular Pathways
- Cytokine Signaling Pathways and Interactions
- DNA Repair Mechanisms
- Cell death mechanisms and regulation
- Pancreatic and Hepatic Oncology Research
- Advanced Breast Cancer Therapies
- NF-κB Signaling Pathways
- Chromatin Remodeling and Cancer
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Retinoids in leukemia and cellular processes
- Computational Drug Discovery Methods
- PARP inhibition in cancer therapy
- RNA Interference and Gene Delivery
- Click Chemistry and Applications
- Genomics and Chromatin Dynamics
- HIV/AIDS drug development and treatment
- Autophagy in Disease and Therapy
- Viral Infectious Diseases and Gene Expression in Insects
- Chronic Myeloid Leukemia Treatments
Johannes Gutenberg University Mainz
2016-2025
University Medical Center of the Johannes Gutenberg University Mainz
2016-2025
Friedrich Schiller University Jena
2006-2022
Aswan University
2022
Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie
2018
University of Rostock
2018
Carl von Ossietzky Universität Oldenburg
2016
Ludwig Boltzmann Institute for Cancer Research
2015
Medical University of Vienna
2015
University Hospital and Clinics
2015
Cytokines such as interferons (IFNs) activate signal transducers and activators of transcription (STATs) via phosphorylation. Histone deacetylases (HDACs) the histone acetyltransferase (HAT) CBP dynamically regulate STAT1 acetylation. Here we show that acetylation counteracts IFN-induced phosphorylation, nuclear translocation, DNA binding, target gene expression. Biochemical genetic experiments altering HAT/HDAC activity ratio mutants reveal a phospho-acetyl switch regulates signaling CBP,...
Acetylation of signaling molecules can lead to apoptosis or differentiation carcinoma cells. The molecular mechanisms underlying these processes and the biological role enzymes mediating transfer removal an acetyl-group are currently under intense investigation. Our study shows that Stat1 is acetylated protein. acetylation depends on balance between Stat1-associated histone deacetylases (HDACs) acetyltransferases (HATs) such as CBP. Remarkably both inhibitors HDACs cytokine interferon α...
Abstract BACKGROUND Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, induced in vitro differentiation of primary acute myeloid leukemia (AML) blasts, an effect enhanced by all‐trans retinoic (ATRA). Clinical responses to VPA were recently observed patients with myelodysplastic syndrome (MDS). Herein, the authors have described results clinical trial plus ATRA 26 poor‐risk AML. METHODS (5–10 mg/kg starting dose) and (45 mg/m 2 ) administered orally. Low‐dose AraC or hydroxyurea...
Abstract Prostate cancer (PCa) is the most prevalent in men. Hyperactive STAT3 thought to be oncogenic PCa. However, targeting of IL-6/STAT3 axis PCa patients has failed provide therapeutic benefit. Here we show that genetic inactivation Stat3 or IL-6 signalling a Pten -deficient mouse model accelerates progression leading metastasis. Mechanistically, identify p19 ARF as direct target. Loss disrupts ARF–Mdm2–p53 tumour suppressor bypassing senescence. Strikingly, also and CDKN2A mutations...
<h3>Background</h3> Activation and differentiation of fibroblasts into contractile protein-expressing myofibroblasts their acquired apoptosis-resistant phenotype are critical factors towards the development idiopathic pulmonary fibrosis (IPF), a fatal disease characterised by distorted structure excessive extracellular matrix (ECM) deposition. The molecular mechanisms underlying these processes in IPF remain incompletely understood. We investigated possible implication aberrant...
Survivin appears to function as an apoptosis inhibitor and a regulator of cell division during development tumorigenesis. Here we report the molecular characterization nucleocytoplasmic transport survivin its potential implications for We identified evolutionary conserved Crm1-dependent nuclear export signal (NES) in survivin. In dividing cells, NES is essential tethering survivin/Aurora-B kinase complex mitotic machinery, which turn be proper division. addition, seems required...
Histone deacetylase inhibitors (HDACi) are promising antineoplastic agents, but their precise mechanisms of actions not well understood. In particular, the relevance p53 for HDACi-induced effects has been fully elucidated. We investigated anticancer four structurally distinct HDACi, vorinostat, entinostat, apicidin and valproic acid, using isogenic HCT-116 colon cancer cell lines differing in status.Effects were assessed by MTT assay, flow-cytometric analyses propidium iodide uptake,...
DNA-damaging anticancer drugs remain a part of metastatic melanoma therapy. Epigenetic reprogramming caused by increased histone deacetylase (HDAC) activity arising during tumor formation may contribute to resistance melanomas the alkylating temozolomide, dacarbazine, and fotemustine. Here, we report on impact class I HDACs response malignant cells treated with agents. The data show that in situ contain high level HDAC1/2 overexpress HDAC1/2/3 compared noncancer cells. Furthermore,...
Checkpoint kinases sense replicative stress to prevent DNA damage. Here we show that the histone deacetylases HDAC1/HDAC2 sustain phosphorylation of checkpoint ATM, CHK1 and CHK2, activity cell cycle gatekeeper WEE1 CDK1, induction tumour suppressor p53 in response stalled replication. Consequently, HDAC inhibition upon promotes mitotic catastrophe. Mechanistically, HDAC1 HDAC2 suppress expression PPP2R3A/PR130, a regulatory subunit trimeric serine/threonine phosphatase 2 (PP2A). Genetic...
Epigenetic modifiers of the histone deacetylase (HDAC) family contribute to autoimmunity, cancer, HIV infection, inflammation, and neurodegeneration. Hence, inhibitors (HDACi), which alter protein acetylation, gene expression patterns, cell fate decisions, represent promising new drugs for therapy these diseases. Whereas pan-HDACi inhibit all 11 Zn2+-dependent deacetylases (HDACs) cause a broad spectrum side effects, specific 6 (HDAC6i) are supposed have less effects. We present synthesis...