A5040391300- Hippo pathway signaling and YAP/TAZ
- Plant nutrient uptake and metabolism
- Phytase and its Applications
- GABA and Rice Research
- Chromosomal and Genetic Variations
- Plant Molecular Biology Research
- Plant tissue culture and regeneration
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- RNA Research and Splicing
- Plant Surface Properties and Treatments
- Pancreatic and Hepatic Oncology Research
- Biotechnology and Related Fields
- Renal and related cancers
- Plant Genetic and Mutation Studies
- Horticultural and Viticultural Research
- Hemoglobinopathies and Related Disorders
- Signaling Pathways in Disease
- Plant Virus Research Studies
- Plant Gene Expression Analysis
- Cancer Mechanisms and Therapy
- Biochemical and Molecular Research
- Cancer-related molecular mechanisms research
- Chromatin Remodeling and Cancer
- Cancer Genomics and Diagnostics
Cold Spring Harbor Laboratory
2011-2024
University of Crete
2004-2009
Abstract Glutamate dehydrogenase (GDH) may be a stress-responsive enzyme, as GDH exhibits considerable thermal stability, and de novo synthesis of the α-GDH subunit is induced by exogenous ammonium senescence. NaCl treatment induces reactive oxygen species (ROS), intracellular ammonia, expression tobacco (Nicotiana tabacum cv Xanthi) gdh-NAD;A1 encoding α-subunit GDH, increase in immunoreactive α-polypeptide, assembly anionic isoenzymes, vitro aminating activity tissues from hypergeous plant...
Abstract Mobile small RNAs serve as local positional signals in development and coordinate stress responses across the plant. Despite its central importance, an understanding of how cell-to-cell movement is governed lacking. Here, we show that miRNA mobility precisely regulated through a gating mechanism polarised at defined cell–cell interfaces. This generates directional between neighbouring cells limits long-distance shoot-to-root trafficking, underpins domain-autonomous behaviours within...
In higher plants the glutamate dehydrogenase (GDH) enzyme catalyzes reversible amination of 2-oxoglutarate to form glutamate, using ammonium as a substrate. For better understanding physiological function GDH either in assimilation or supply 2-oxoglutarate, we used transgenic tobacco (Nicotiana tabacum L.) overexpressing two genes encoding enzyme. An vivo real time (15)N-nuclear magnetic resonance (NMR) spectroscopy approach allowed demonstration that, when were overexpressed individually...
The Hippo signaling pathway is commonly dysregulated in human cancer, which leads to a powerful tumor dependency on the YAP/TAZ transcriptional coactivators. Here, we used paralog co-targeting CRISPR screens identify kinases MARK2/3 as absolute catalytic requirements for function diverse carcinoma and sarcoma contexts. Underlying this observation direct MARK2/3-dependent phosphorylation of NF2 YAP/TAZ, effectively reverses suppressive activity module LATS1/2. To simulate targeting MARK2/3,...
Following the discovery of glutamine synthetase/glutamate (Glu) synthase, physiological roles Glu dehydrogenase (GDH) in nitrogen metabolism plants remain obscure and is subject considerable controversy. Recently, transgenics were used to overexpress gene encoding for beta-subunit polypeptide GDH, resulting GDH-isoenzyme 1 deaminating vivo Glu. In this work, we present transgenic tobacco (Nicotiana tabacum) overexpressing plant gdh alpha-subunit GDH. The levels transcript correlated well...
Recurrent chromosomal rearrangements found in rhabdomyosarcoma (RMS) produce the PAX3–FOXO1 fusion protein, which is an oncogenic driver and a dependency this disease. One important function of to arrest myogenic differentiation, linked ability RMS cells gain unlimited proliferation potential. Here, we developed phenotypic screening strategy for identifying factors that collaborate with block myo-differentiation RMS. Unlike most genes evaluated our screen, loss any three subunits Nuclear...
An enhanced requirement for nutrients is a hallmark property of cancer cells. Here, we optimized an in vivo genetic screening strategy acute myeloid leukemia (AML), which led to the identification myo-inositol transporter SLC5A3 as dependency this disease. We demonstrate that essential support auxotrophy AML. The commonality among SLC5A3-dependent AML lines transcriptional silencing ISYNA1, encodes rate-limiting enzyme biosynthesis, inositol-3-phosphate synthase 1. use gain- and...
The presence of basal lineage characteristics signifies hyper-aggressive human adenocarcinomas the breast, bladder, and pancreas. However, biochemical mechanisms that maintain this aberrant cell state are poorly understood. Here we performed marker-based genetic screens in search factors needed to identity pancreatic ductal adenocarcinoma (PDAC). This approach revealed MED12 as a powerful regulator disease. Using reconstitution epigenomics, show carries out function by bridging transcription...
Abstract The Hippo signaling pathway is commonly dysregulated in human cancer, which leads to a powerful tumor dependency on the YAP/TAZ transcriptional coactivators. Here, we used paralog co-targeting CRISPR screens identify kinases MARK2/3 as absolute catalytic requirements for function diverse carcinoma and sarcoma contexts. Underlying this observation direct MARK2/3-dependent phosphorylation of NF2 YAP/TAZ, effectively reverses suppressive activity module LATS1/2. To simulate targeting...
<p>A, IP–western blot analysis evaluating the interaction between 14-3-3e and YAPWT YAP5D mutants or TAZWT TAZ4D in HEK-293T cells. Aspartate mutant reversion to wild-type S/T is indicated. Data are representative of two independent experiments. B, mRNA expression log2 fold-change YAP/TAZ target genes (n=78 significantly downregulated upon YAP/TAZdKO upregulated expression) following YAP overexpression compared Ctrl RH-30 n=2 C, Rescue experiment MARK2+3dKO lentiviral shown mean ± SD...
<p>A, Growth kinetics of subcutaneous YAPC xenografts implanted in immunodeficient mice. Indicated genes were knocked out just before injection. Data are shown as mean ± SEM n=5 per group. P values calculated using a mixed effects model (considering the interaction experimental groups over time) compared to Ctrl group and corrected with Bonferroni-Holm (BH). B, Tumor imaging at end-point xenograft experiments A. C, mRNA expression MARK1-4 different tissues. from Genotype-Tissue...
<p>A,B, CRISPR screening results from 22 cancer cell lines. A, Abundance fold-change of positive controls (dgRNAs targeting essential genes n=28 paired with control) and negative non-coding regions n=54 nontargeting dgRNAs n=97). Data are shown as mean ± SD B, MARK2+3. Each dot represents a single dgRNA. n=24 dgRNAs. C, Pearson correlation analysis data comparing log2 fold-changes double gene knockout published replicate experiments. Functional domain class libraries indicated. R2...