A5089700251- RNA Research and Splicing
- Virus-based gene therapy research
- RNA and protein synthesis mechanisms
- Mast cells and histamine
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- RNA modifications and cancer
- HIV Research and Treatment
- Hepatitis B Virus Studies
- PI3K/AKT/mTOR signaling in cancer
- RNA Interference and Gene Delivery
- Animal Virus Infections Studies
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- Acute Myeloid Leukemia Research
- T-cell and Retrovirus Studies
- Herpesvirus Infections and Treatments
- Cancer-related Molecular Pathways
- RNA regulation and disease
- Chronic Lymphocytic Leukemia Research
- Signaling Pathways in Disease
- interferon and immune responses
- Cancer-related gene regulation
- Cell Adhesion Molecules Research
- 14-3-3 protein interactions
University of Basel
2003-2019
UCLouvain
1994
Ludwig Cancer Research
1994
Tufts University
1991
Friedrich Miescher Institute
1975-1989
National Cancer Institute
1981
Salk Institute for Biological Studies
1972
Highly glycolytic cancer cells prevent intracellular acidification by excreting the end-products lactate and H+ via monocarboxylate transporters 1 (MCT1) 4 (MCT4). We report that syrosingopine, an anti-hypertensive drug, is a dual MCT1 MCT4 inhibitor (with 60-fold higher potency on MCT4) prevents efflux. Syrosingopine elicits synthetic lethality with metformin, of mitochondrial NADH dehydrogenase. NAD+, required for ATP-generating steps glycolysis, regenerated from dehydrogenase or treatment...
The spontaneous leukemias of AKR mice are caused by mink cell focus-forming (MCF) viruses. These viruses generated recombination between several endogenous murine retroviruses. virological events leading to the generation leukemogenic agent were investigated using an oligonucleotide specific for U3 region virus and env-reactive probes different classes leukemia virus. It was shown that (i) MCF is formed at least three sequences; (ii) donor inducible xenotropic Bxv-1; (iii) all tumors contain...
AU-rich elements (ARE) present in the 3′ untranslated regions of many cytokines and immediate-early genes are responsible for targeting transcripts rapid decay. We evidence from cotransfection experiments NIH 3T3 cells that two signaling pathways, one involving phosphatidylinositol 3-kinase (PI3-K), p38 mitogen-activated protein kinase (MAPK), lead to stabilization interleukin-3 mRNA parallel. Stabilization mediated by either pathways was antagonized tristetraprolin (TTP), an AU-binding...
Interleukin 3 (IL-3) is transiently produced by murine bone marrow-derived mast cells in response to antigen stimulation of the high-affinity immunoglobulin E receptors. We have studied postreceptor signaling pathways involved regulating expression IL-3 gene cell line PB-3c. Large amounts mRNA accumulated after exposure calcium ionophore A23187, a reagent that increases intracellular Ca2+. Phorbol 12-myristate 13-acetate, which stimulates protein kinase C, did not induce accumulation,...
Control of mRNA stability is critical for expression short-lived transcripts from cytokines and proto-oncogenes. Regulation involves an AU-rich element (ARE) in the 3' untranslated region (3'UTR) cognate trans-acting factors thought to promote either degradation or stabilization mRNA. In this study we present a novel approach using somatic cell genetics designed identify regulators interleukin-3 (IL-3) turnover. Mutant lines were generated diploid HT1080 cells transfected with reporter...
Beta-catenin plays an essential role in several biological events including cell fate determination, proliferation, and transformation. Here we report that beta-catenin is encoded by a labile transcript whose half-life prolonged Wnt phosphatidylinositol 3-kinase-AKT signaling. AKT phosphorylates the mRNA decay-promoting factor KSRP at unique serine residue, induces its association with multifunctional protein 14-3-3, prevents interaction exoribonucleolytic complex exosome. This impairs...
Tumor necrosis factor alpha (TNF-α) expression is regulated by transcriptional as well posttranscriptional mechanisms, the latter including control of mRNA decay through an AU-rich element (ARE) in 3′ untranslated region (UTR). Using two mutant cell lines deficient for ARE-mediated decay, we provide evidence a second element, constitutive (CDE), which also located UTR TNF-α. In stably transfected RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS), CDE continues to target reporter...
AU-rich elements within the 3' untranslated region of transcripts lymphokines and some protooncogenes serve as signal for rapid mRNA degradation. By using an AUUUA matrix, we have affinity-purified a 32-kDa protein, microsequenced it, cloned corresponding cDNA. In vitro, recombinant protein bound specifically to transcripts, including those interleukin 3, granulocyte/macrophage colony-stimulating factor, c-fos, c-myc. Sequence analysis revealed unexpected homology enoyl-CoA hydratase (EC...
Synthetic lethality between the clinically approved noncancer drugs metformin and syrosingopine specifically kills cancer cells.
In mast cells, expression of interleukin-3 (IL-3) is induced following IgE-receptor activation via calcium-dependent mRNA stabilization. We performed a mutational analysis the 8 AUUUA motifs located in 3'-untranslated region IL-3 mRNA, and analyzed effect on stability PB-3c cells. Similar to endogenous exogenous transcripts had short half-life were stabilized stimulation calcium influx by ionomycin. Specific mutation 3 almost same stabilizing as deletion entire AU-rich region. Mutating even...
Vascular endothelial growth factor (VEGF) is one of the most important regulators physiological and pathological angiogenesis. Constitutive activation extracellular signal-regulated kinase (ERK) pathway overexpression VEGF are common denominators tumors from different origins. We have established a new link between these two fundamental observations converging on mRNA stability. In this complex phenomenon, tristetraprolin (TTP), an adenylate uridylate-rich element-associated protein that...
BRF1 posttranscriptionally regulates mRNA levels by targeting ARE-bearing transcripts to the decay machinery. We previously showed that protein kinase B (PKB) phosphorylates at Ser92, resulting in binding 14-3-3 and impairment of activity. Here we identify an additional regulatory site Ser203 cooperates vivo with Ser92. In vitro labeling wortmannin sensitivity indicate phosphorylation is also performed PKB. Mutation both serines alanine uncouples from PKB regulation, leading constitutive...