Albert Tauler

Albert Tauler
University of Barcelona | UB · Department of Biochemistry and Molecular Biology (Faculty of Pharmacy)

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66
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Publications (66)
Chapter
The detection of autophagic vesicles in interphase cells is well characterized with markers such as LC3, SQSTM1 (also known as p62) and LAMP2, which are commonly used in immunofluorescence and biochemistry assays to evaluate the status of autophagy in adherent cells. During mitosis, cells undergo important morphological changes which alter the posi...
Chapter
Chromosomal instability (CIN) is a hallmark of cancer, which is characterized by the gain or loss of chromosomes as well as the rearrangement of the genetic material during cell division. Detection of mitotic errors such as misaligned chromosomes or chromosomal bridges (also known as lagging chromosomes) is challenging as it requires the analysis a...
Article
Ribosomes execute the transcriptional program in every cell. Critical to sustain nearly all cellular activities, ribosome biogenesis requires the translation of ~200 factors of which 80 are ribosomal proteins (RPs). As ribosome synthesis depends on RP mRNA translation, a priority within the translatome architecture should exist to ensure the preser...
Article
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Lysosomes, as primary degradative organelles, are the endpoint of different converging pathways, including macroautophagy. To date, lysosome degradative function has been mainly studied in interphase cells, while their role during mitosis remains controversial. Mitosis dictates the faithful transmission of genetic material among generations, and pe...
Article
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Many oncogenes enhance nucleotide usage to increase ribosome content, DNA replication, and cell proliferation, but in parallel trigger p53 activation. Both the impaired ribosome biogenesis checkpoint (IRBC) and the DNA damage response (DDR) have been implicated in p53 activation following nucleotide depletion. However, it is difficult to reconcile...
Preprint
Lysosomes, as primary degradative organelles, are the end-point of different converging pathways including macroautophagy. To date, lysosome function has mainly focused on interphase cells, while their role during mitosis remains controversial. Mitosis dictates the faithful transmission of genetic material among generations, and perturbations of mi...
Article
Full-text available
Cancer cells rely on mTORC1 activity to coordinate mitogenic signaling with nutrients availability for growth. Based on the metabolic function of E2F1, we hypothesize that glucose catabolism driven by E2F1 could participate on mTORC1 activation. Here, we demonstrate that glucose potentiates E2F1-induced mTORC1 activation by promoting mTORC1 translo...
Article
The role of MYC in regulating p53 stability as a function of increased ribosome biogenesis is controversial. On the one hand, it was suggested that MYC drives the overexpression of ribosomal proteins (RP)L5 and RPL11, which bind and inhibit HDM2, stabilizing p53. On the other, it has been proposed that increased ribosome biogenesis leads the consum...
Article
Ribosomal protein (RP) expression in higher eukaryotes is regulated translationally through the 5′TOP sequence. This mechanism evolved to more rapidly produce RPs on demand in different tissues. Here we show that 40S ribosomes, in a complex with the mRNA binding protein LARP1, selectively stabilize 5′TOP mRNAs, with disruption of this complex leadi...
Article
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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 in high mortality rates and high incidence of relapse. With the intent to find new therapies for neuroblastomas, we in...
Article
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In addition to being a master regulator of cell cycle progression, E2F1 regulates other associated biological processes, including growth and malignancy. Here, we uncover a regulatory network linking E2F1 to lysosomal trafficking and mTORC1 signaling that involves v-ATPase regulation. By immunofluorescence and time-lapse microscopy we found that E2...
Article
In the past, the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) has been shown to induce apoptosis in several human tumor types, including neuroblastomas. Amplification and over-expression of the MYCN oncogene is a diagnostic hallmark and a poor prognostic indicator in high-risk neuroblastomas. Here, we studied the relationship between MYCN...
Article
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Type 2 diabetes mellitus (T2DM) is a worldwide heath problem that is characterized by insulin resistance and the eventual loss of β cell function. As recent studies have shown that loss of ribosomal protein (RP) S6 kinase 1 (S6K1) increases systemic insulin sensitivity, S6K1 inhibitors are being pursued as potential agents for improving insulin res...
Article
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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 and SK-N-JD neuroblastoma stable cell lines. In these cells, the ER-E2F1 fusion protein is expressed in the cytosol; the addition of 4-hydroxytamoxifen (OHT) induces its translocation...
Data
CT99021 inhibits ROS production and Bax activation induced by E2F1. (A) PC12 ER-E2F1 cells were serum-deprived and treated with (+) or without (−) OHT in the presence (+) or in the absence (−) of 10 µM CT99021 for 4 hours. ROS levels were analysed by using the oxidation-sensitive fluorescent probe H2DCFDA. Results are presented as Mean ± SEM, for n...
Data
List of genes that are included on the Human Oxidative Stress and Antioxidant Defense RT2 Profiler PCR Array (Biosciences). (DOCX)
Data
mRNA changes after OHT addition in SK-N-JD cells.- RT2Profiler human oxidative stress and antioxidant defense PCR Arrays (Bioscience) were performed according to the manufacture’s protocols. Expression levels were compared between with and without OHT addition. Hypoxanthine phosphoribosyltransferase 1 gene was used as control for each gene expressi...
Article
Neuroblastoma (NB) is the most common solid extracranial tumor in children. Here we showed that trichostatin A, a histone deacetylase inhibitor (HDACi), decreases cell viability in three NB cell lines of different phenotypes. The treatment leads to G2/M-phase arrest, apoptosis and autophagy. Autophagy induction accompanies apoptosis in the most pro...
Data
Effect of tamoxifen on E2F3 transcriptional activity. U2OS cells were transient transfected with ER-E2F3 and [E2F]3-Luc vectors. After serum-starved, cells were treated with OHT (+) or not (−) for 12 h and luciferase activity was measured for both conditions. Statistically significant differences were obtained by comparison with untreated cells. (D...
Data
Effect of rapamycin on the expression levels and translocation of ER-E2F1 to the nucleus. Stable ER-E2F1 U2OS cells were serum-starved and treated with OHT (+) or not (−) for 6 hours (OHT) in the presence or in the absence of rapamycin (rap). (A) Expression of the indicated proteins was determined by Western blot analysis. (B) Cells were immunostai...
Article
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During cell proliferation, growth must occur to maintain homeostatic cell size. Here we show that E2F1 is capable of inducing growth by regulating mTORC1 activity. The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1's ability to bind DNA and to regulate gene transcription, demonstrating that a gene induction expression progra...
Article
Multiple E2F1 phosphorylation sites have been described as targets of different kinases, yet their in vivo implication is uncertain. We previously reported that GSK3beta is able to phosphorylate E2F1 in vitro at Ser403 and Ser433. Recently, it has been shown that both residues are also direct targets of p38 MAP kinase. In order to determine whether...
Article
Mitogenic response to growth factors is concomitant with the modulation they exert on the levels of Fructose 2,6-bisphosphate (Fru-2,6-P2), an essential activator of the glycolytic flux. In mammalian cells, decreased Fru-2,6-P2 concentration causes cell cycle delay, whereas high levels of Fru-2,6-P2 sensitize cells to apoptosis. In order to analyze...
Article
Both E2F1 and GSK3beta have been described as essential targets in neuronal apoptosis. Previous studies have demonstrated that GSK3beta binds to E2F1 in vivo. We wanted to investigate whether these proteins could share a common apoptotic signal pathway in neuronal cells. With this intention, we developed a PC12 ER-E2F1 stable cell line in which E2F...
Article
GSK3beta and E2F1 play an important role in the control of proliferation and apoptosis. Previous work has demonstrated that GSK3beta indirectly regulates E2F activity through modulation of cyclin D1 levels. In this work we show that GSK3beta phosphorylates human E2F1 in vitro at serine 403 and threonine 433, both residues localized at its transacti...
Chapter
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The technology of UniTargetingResearch AS (UTRtech™) is based on the finding that the efficiency of directing mRNA to the endoplasmic reticulum is influenced by targeting signals. Using selected signals, genetically engineered mammalian cells are generated from which a protein of interest can be efficiently secreted. An industrial collaboration has...
Article
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In the present study, we demonstrate that E2F is implicated in the regulation of the glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (6PF2K/Fru-2,6-BPase) during cell division. The expression of this enzyme is induced during the G(1)/S transition of the cell cycle. We identified and monitored the E2F-pocket protein complexes...
Article
In the present study, we demonstrate that E2F is implicated in the regulation of the glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (6PF2K/Fru-2,6-BPase) during cell division. The expression of this enzyme is induced during the G(1)/S transition of the cell cycle. We identified and monitored the E2F-pocket protein complexes...
Article
The expression of F-type 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is rapidly induced by growth factors. We report here that an AP-1 intragenic sequence located at position +612 of the F-type 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase transcription initiation site is involved in the transcriptional activation of this gene by se...
Article
In the chicken intestine, the reduction in Na(+) intake led to a decrease in the transport of alpha-methyl-D-glucoside in the ileum (reduction of 42%) and in the rectum (51%). These reductions were reversed within 24 h after resalination and were inversely correlated to the changes in aldosterone plasma concentration. The reduction in intestinal he...
Article
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The hepatic isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PF2K/Fru-2,6-BPase) is transcriptionally stimulated by glucocorticoids, whereas insulin blocks this stimulatory effect. Although this inhibitory effect has been extensively reported, nothing is known about the signalling pathway responsible. We have used well-characterized...
Article
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Previous studies have demonstrated that the F isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase(6PF2K/Fru-2,6-BPase) is transcriptionally regulated by growth factors. The aim of this study was to investigate the importance of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway in the regulation of 6PF2K/Fru-2,6-BPase gene expressi...
Article
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Modification of muscular contractile patterns by denervation and chronic low frequency stimulation induces structural, physiological, and biochemical alterations in fast twitch skeletal muscles. Fructose 2,6-bisphosphate is a potent activator of 6-phosphofructo-1-kinase, a key regulatory enzyme of glycolysis in animal tissues. The concentration of...
Article
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Secretion of an intracellular protein from a cell factory requires as a first step the redirection of the mRNA for synthesis of the protein on the endoplasmic reticulum. The feasibility of retargeting a mRNA coding for an intracellular protein to the endoplasmic reticulum was investigated using Ltk- fibroblasts stably transfected with gene construc...
Article
Full-text available
To study the mechanism that controls fructose-2,6-bisphosphate (Fru-2,6-P2) accumulation, as well as the mRNAs levels of the glycolytic/gluconeogenic regulatory enzymes in the livers of fed and starved lean (fa/-) and obese (fa/fa) Zucker rats. Rats were fed a standard chow or deprived of food for 24 h. Male lean (fa/-) and genetically obese (fa/fa...
Article
The expression of the F-type 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase mRNA was studied during liver regeneration by three independent assays: Northern blot analysis, reverse transcription-polymerase chain reaction and ribonuclease protection. We demonstrate the presence of F-type mRNA in foetal and adult rat livers and a transient incre...
Article
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The activation of glycolytic flux is a biochemical characteristic of growing cells. Several reports have demonstrated the role of fructose 2,6-bisphosphate in this process. In this paper we show that the levels of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (6PF2K/Fru-2,6-P2ase) mRNA are modulated in response to serum and growth factors an...
Article
Full-text available
Hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-beta) are believed to be of major importance for hepatic regeneration after liver damage. We have studied the effect of these growth factors on fructose 2,6-bisphosphate (Fru-2,6-P2) levels and the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (6PF2K/Fru-2,...
Article
Using an established sequential detergent/salt extraction technique, with minor modifications, the total polysomes in CHO cells have been separated into free, cytoskeletal-bound and membrane-bound populations. Sucrose gradient sedimentation analysis showed that a very high percentage of ribosomes were in polysomes in all three fractions, indicating...
Article
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The effect of cyclic AMP (cAMP)-dependent phosphorylation and ADP-ribosylation on the activities of the rat liver bifunctional enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), was investigated in order to determine the role of the N-terminus in covalent modification of the enzyme. The bifunctional enzyme was demonstrat...
Article
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Levels of mRNA for mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase, carnitine palmitoyltransferase I (CPT I) and carnitine palmitoyltransferase II (CPT II), fatty acid synthase (FAS) and actin were analysed during liver regeneration. mRNA levels for mitochondrial HMG-CoA synthase decreased rapidly, reaching a minimum 12 h after part...
Article
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The control of hepatic 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase gene expression by glucagon was studied. Intraperitoneal administration of glucagon rapidly decreased the fructose 2,6-bisphosphate content by phosphorylation of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase and diminution of its Vmax. Immunologic studies using a spe...
Article
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Levels of mRNA for glucokinase, L-pyruvate kinase, fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase were analysed during liver regeneration. Levels of mRNA for glycolytic enzymes (glucokinase and L-pyruvate kinase) decreased rapidly after partial hepatectomy. Glucokinase mRNA increased at 16-24 h, returning to normal values after t...
Article
Levels of mRNA for glucokinase, L-pyruvate kinase, fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxy-kinase were analysed during liver regeneration. Levels of mRNA for glycolytic enzymes (glucokinase and L-pyruvate kinase) decreased rapidly after partial hepatectomy. Glucokinase mRNA increased at 16-24 h, returning to normal values after...
Article
Full-text available
The control of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2; EC 2.7.1.105/3.1.3.46) gene expression during liver regeneration was studied. The level of PFK-2/FBPase-2 mRNA decreased to about 5% of the control value 6 hr after partial hepatectomy. Thereafter the mRNA increased to a maximum at 48 hr and returned to normal leve...
Chapter
Full-text available
Fructose 2,6-bisphosphate (Fru-2,6-P2) is a potent stimulator of 6-phosphofructo 1-kinase which has been identified in all eukaryotic cells. Its synthesis and breakdown are catalyzed by 6-phosphofructo 2-kinase (PFK-2) and fructose 2,6-bisphosphatase (FBPase-2), respectively. These two activities belong to separate domains of the same homodimeric p...
Article
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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 the role of two putative bisphosphatase active site histidyl residues in catalysis. His-258 has...
Article
Rat liver glucokinase was expressed in Escherichia coli by using an expression system based on bacteriophage T7 RNA polymerase. The expressed protein starts with the predicted initiator methionine residue and ends at the appropriate carboxyl terminal residue. It was partially purified by ammonium sulfate precipitation and gel filtration and had kin...
Article
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. T...
Article
Dexamethasone addition to cultured hepatocytes caused a 90-fold increase in mRNA for 6-phosphofructo 2-kinase/fructose-2,6-bisphosphatase. Glucocorticoid administration in vivo also increased the enzyme's mRNA in skeletal muscle by 3-4-fold. The sequence of the 5'-flanking region of the enzyme's gene revealed at least one consensus glucocorticoid r...
Article
Full-text available
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 and the bisphosphatase activities of the bifunctional enzyme to about 30% of the values in livers of normal rats. Triamcinolone treatment restored both activit...
Article
Full-text available
The effects of fasting/refeeding and untreated or insulin-treated diabetes on the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase and its mRNA in rat liver were determined. Both enzymatic activities fell to 20% of control values with fasting or streptozotocin-induced diabetes and were coordinately restored to normal within...
Article
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. The protein was efficiently expressed (i) as a fusion protein that starts at the T7 major capsid protein initiatio...
Article
Full-text available
The bisphosphatase domain of the rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase has been shown to exhibit a structural similarity to yeast phosphoglycerate mutase and human red blood cell 2,3-bisphosphoglycerate mutase including very similar active site sequences with a histidyl residue being involved in phospho group transfer. The...
Article
1. Four enzymes with phosphoglycolate phosphatase (EC 3.1.3.18) activity have been detected in extracts of chicken skeletal muscle and liver analyzed by gel-filtration and ion-exchange chromatography. 2. Two enzymes have been found in muscle extracts. One of them acts on glycerate 2,3-P2, in addition to glycolate 2-P. 3. Liver extracts contain two...
Article
2,3-Bisphosphoglycerate synthase-phosphatase and the hybrid phosphoglycerate mutase/2,3-bisphosphoglycerate synthase-phosphatase have been partially purified from pig brain. Their 2,3-bisphosphoglycerate synthase, 2,3-bisphosphoglycerate phosphatase and phosphoglycerate mutase activities are concurrently lost upon heating and treatment with reagent...
Article
1.1. The levels of glycerate 2,3-P2 and of 2,3-bisphosphoglycerate synthase and 2,3-bisphosphoglycerate phosphatase activities have been determined in isolated rat hepatocytes and adipocytes and in perfused rat tissues to discard blood contamination.2.2. The values obtained are much lower than those previously reported, ranging 0.50–40 nmol/g tissu...
Article
Histidine, arginine and lysine residues are essential for the multifunctional 2,3-bisphosphoglycerate synthase-phosphatase purified from pig skeletal muscle. The synthase, phosphatase and phosphoglycerate mutase activities of the enzyme are concurrently lost upon treatment with diethylpyrocarbonate, phenylglyoxal and trinitrobenzenesulfonate. The p...
Article
1. 1. The levels of the enzymes involved in the metabolism of glycerate-2,3-P2 (phosphoglycerate mutase, bisphosphoglycerate synthase-phosphatase and bisphosphoglycerate phosphatase) in cat and in pig tissues are different. 2. 2. The main difference is the low level of bisphosphoglycerate synthase-phosphatase in cat tissues. 3. 3. As a consequence,...
Article
The enzymes with 2,3-bisphosphoglycerate synthase and 2,3-bisphosphoglycerate phosphatase activity present in pig and in cat tissues have been isolated and partially characterized. It is concluded that regulation of 2,3-bisphosphoglycerate metabolism differ in erythrocytes and in tissue cells.
Article
1.1. Type M phosphoglycerate mutase and skeletal muscle bisphosphoglycerate synthasephosphatase from pig are similarly affected by Hg2+.2.2. Both enzymes lose the phosphoglycerate mutase and the glycerate-2,3-P2 synthase activities, and increase the glycerate-2,3-P2 phosphatase activity upon Hg2+-treatment.3.3. In contrast, bisphosphoglycerate phos...

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