A5065080458- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Pancreatic function and diabetes
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Enzyme Structure and Function
- PI3K/AKT/mTOR signaling in cancer
- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- Diet, Metabolism, and Disease
- Neuroblastoma Research and Treatments
- Liver physiology and pathology
- DNA Repair Mechanisms
- Muscle metabolism and nutrition
- Cell death mechanisms and regulation
- Protein Kinase Regulation and GTPase Signaling
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Enzyme function and inhibition
- Endoplasmic Reticulum Stress and Disease
- RNA Research and Splicing
- Biochemical effects in animals
- Ubiquitin and proteasome pathways
Institut d'Investigació Biomédica de Bellvitge
2012-2022
Universitat de Barcelona
2006-2021
Bellvitge University Hospital
1995-2019
Duran i Reynals Hospital
2015-2016
State University of New York
1987-1990
Stony Brook School
1990
Stony Brook University
1988-1989
Vanderbilt University
1988-1989
During cell proliferation, growth must occur to maintain homeostatic size. Here we show that E2F1 is capable of inducing by regulating mTORC1 activity. The activation and dependent on both E2F1's ability bind DNA regulate gene transcription, demonstrating a induction expression program required in this process. Unlike E2F1, E2F3 unable activate mTORC1, suggesting activity could be restricted individual E2F members. effect the does not depend Akt. Furthermore, over-expression TSC2 interfere...
Neuroblastoma is a malignant embryonal tumor occurring in young children, consisting of undifferentiated neuroectodermal cells derived from the neural crest. Current therapies for high-risk neuroblastoma are insufficient, resulting high mortality rates and incidence relapse. With intent to find new neuroblastomas, we investigated efficacy low-doses actinomycin D, which at low concentrations preferentially inhibit RNA polymerase I-dependent rRNA trasncription therefore, ribosome biogenesis....
The effects of fasting/refeeding and untreated or insulin-treated diabetes on the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase its mRNA in rat liver were determined. Both enzymatic activities fell to 20% control values with fasting streptozotocin-induced coordinately restored normal within 48 h refeeding 24 insulin administration. These alterations always mirrored by corresponding changes amount as determined phosphoenzyme formation immunoblotting. In contrast,...
Lysosomes, as primary degradative organelles, are the endpoint of different converging pathways, including macroautophagy. To date, lysosome function has been mainly studied in interphase cells, while their role during mitosis remains controversial. Mitosis dictates faithful transmission genetic material among generations, and perturbations mitotic division lead to chromosomal instability, a hallmark cancer. Heretofore, correct progression relies on orchestrated degradation factors, which...
The current model for hepatic 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase divides the protein into two functional domains: an N-terminal kinase domain and a carboxyl-terminal bisphosphatase domain. Site-directed mutagenesis was used to evaluate role of putative active site histidyl residues in catalysis. His-258 has been implicated as phosphoacceptor (Pilkis, S. J., Lively, M. O., El-Maghrabi, R. (1987) J. Biol. Chem. 262, 12672-12675), importance this residue confirmed when it...
Cancer cells rely on mTORC1 activity to coordinate mitogenic signaling with nutrients availability for growth. Based the metabolic function of E2F1, we hypothesize that glucose catabolism driven by E2F1 could participate activation. Here, demonstrate potentiates E2F1-induced activation promoting translocation lysosomes, a process occurs independently AMPK We showed regulates metabolism increasing aerobic glycolysis and identified PFKFB3 regulatory enzyme as an E2F1-regulated gene important...
In addition to being a master regulator of cell cycle progression, E2F1 regulates other associated biological processes, including growth and malignancy. Here, we uncover regulatory network linking lysosomal trafficking mTORC1 signaling that involves v-ATPase regulation. By immunofluorescence time-lapse microscopy found induces the movement lysosomes periphery, this process is essential for E2F1-induced activation repression autophagy. Gain- loss-of-function experiments reveal activity...
Article2 June 2020Open Access Transparent process Nucleotide depletion reveals the impaired ribosome biogenesis checkpoint as a barrier against DNA damage Joffrey Pelletier Corresponding Author [email protected] orcid.org/0000-0001-9174-044X Laboratory of Cancer Metabolism, ONCOBELL Program, Institut d'Investigació Biomèdica de Bellvitge—IDIBELL, L'Hospitalet Llobregat, Spain Search for more papers by this author Ferran Riaño-Canalias Eugènia Almacellas orcid.org/0000-0002-7726-8430 Caroline...
The role of MYC in regulating p53 stability as a function increased ribosome biogenesis is controversial. On the one hand, it was suggested that drives overexpression ribosomal proteins (RP)L5 and RPL11, which bind inhibit HDM2, stabilizing p53. other, has been proposed leads consumption RPL5/RPL11 into nascent ribosomes, reducing levels enhancing tumorigenesis. Here, we show components make up recently described impaired checkpoint (IRBC) complex, RPL5, 5S rRNA, are reduced following...
The mTOR-LARP1-5′TOP axis acts at the translational level as a primary guardian of anabolic capacity cell.
Type 2 diabetes mellitus (T2DM) is a worldwide heath problem that characterized by insulin resistance and the eventual loss of β cell function. As recent studies have shown ribosomal protein (RP) S6 kinase 1 (S6K1) increases systemic sensitivity, S6K1 inhibitors are being pursued as potential agents for improving resistance. Here we found deficiency in mice also leads to decreased growth, intrauterine growth restriction (IUGR), impaired placental development. IUGR common complication human...
Levels of mRNA for glucokinase, L-pyruvate kinase, fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase were analysed during liver regeneration. glycolytic enzymes (glucokinase kinase) decreased rapidly after partial hepatectomy. Glucokinase increased at 16-24 h, returning to normal values this time. kinase recovered control levels 168 h. In contrast, resection remained high the regenerative process. However, not modified significantly. These results correlate with reported rate...
The fructose-2,6-bisphosphatase domain of rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (EC 2.7.105/EC 3.1.3.46) was expressed in Escherichia coli by using an expression system based on bacteriophage T7 RNA polymerase. protein efficiently (i) as a fusion that starts at the major capsid initiation site pET vector and (ii) within bisphosphatase sequence translation reinitiation. Both proteins have similar properties. purified to homogeneity anion-exchange chromatography gel...
Abstract The effect of adrenalectomy and triamcinolone treatment on mRNA encoding rat hepatic 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase was studied. Adrenalectomy decreased both the kinase bisphosphatase activities bifunctional enzyme to about 30% values in livers normal rats. Triamcinolone restored by 24 h. These changes were caused alterations concentration as determined immunoblotting an assay that measures phosphoenzyme formation. Messenger RNA for liver markedly increased...
The rat liver bifunctional enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (ATP:D-fructose-6-phosphate 2-phosphotransferase/D-fructose-2,6-bisphosphate 2-phosphohydrolase, EC 2.7.1.105/EC 3.1.3.46) and its separate kinase domain were expressed in Escherichia coli by using an expression system based on bacteriophage T7 RNA polymerase. enzyme (470 residues per subunit) was efficiently as a protein that starts with the initiator methionine residue ends at carboxyl-terminal tyrosine...
The bisphosphatase domain of the rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase has been shown to exhibit a structural similarity yeast phosphoglycerate mutase and human red blood cell 2,3-bisphosphoglycerate including very similar active site sequences with histidyl residue being involved in phospho group transfer. bifunctional enzyme was found catalyze hydrolysis glycerate 1,3-bisphosphate 3-phosphate inorganic phosphate. Km for 320 microM Vmax 11.5 milliunits/mg....
In this study we demonstrate that accumulation of reactive oxygen species (ROS) is essential for E2F1 mediated apoptosis in ER-E2F1 PC12 pheochromocytoma, and SH-SY5Y SK-N-JD neuroblastoma stable cell lines. these cells, the fusion protein expressed cytosol; addition 4-hydroxytamoxifen (OHT) induces its translocation to nucleus activation E2F1target genes. Previously demonstrated that, OHT treatment induced through caspase-3. Here show caspase-8 activity did not change upon with OHT....
Levels of mRNA for mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase, carnitine palmitoyltransferase I (CPT I) and II II), fatty acid synthase (FAS) actin were analysed during liver regeneration. levels HMG-CoA decreased rapidly, reaching a minimum 12 h after partial hepatectomy returning to normal at 24-36 h. In contrast, CPT I, FAS mRNAs increased throughout the period examined. Expression significantly also as result surgical stress, although effect was much greater. We...