60f Tauler Girona, Albert [WorldCat Identities]
WorldCat Identities

Tauler Girona, Albert

Overview
Works: 47 works in 71 publications in 4 languages and 70 library holdings
Roles: Author
Publication Timeline
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Most widely held works by Albert Tauler Girona
Efecte de la inhibició de les histona desacetilases i d'inductors de p53 en línies cel·lulars de neuroblastoma humà by Constanza Cortés Crignola( Book )

2 editions published between 2014 and 2015 in Catalan and held by 2 WorldCat member libraries worldwide

Els neuroblastomes es caracteritzen per l'heterogeneïtat de les cèl·lules que els composen i la seva capacitat de transdiferenciar entre els diferents fenotips cel·lulars. La freqüència de mutacions en el gen de p53 és molt baixa en el moment de la diagnosi, manifestant-se, normalment, només després del tractament inicial. Aquestes característiques són les causes principals del fracàs dels tractaments actuals contra aquesta neoplàsia. L'objectiud'aquesta tesi ha estat assajarnovesestratègies terapèutiques que poguessin resultar efectives contra tots els tipus cel·lulars, per tal d'evitar l'aparició de recidives. Amb aquesta finalitat, hem decidit utilitzar dues drogues amb eficàcia clínica demostrada. D'una banda, s'ha escollit el SAHA, un inhibidor inespecífic de les HDACs que ha demostrat la seva eficàcia independentment del context de p53; i per l'altra, s'ha seleccionat l'inhibidor de la transcripció actinomicina D, que ha demostrat ser més eficaç contra les cèl·lules que expressen p53. A més, s'ha utilitzat la nutlina-3 com a control per verificar la repercussió de p53 en l'efecte de l'actinomicina D. Aquest treball demostra com aquests fàrmacs disminueixen la viabilitat de totes les línies cel·lulars de neuroblastoma analitzades. El mecanisme i la sensibilitat al tractament observats depenen, tant de la droga utilitzada, com de la línia cel·lular examinada. Així doncs, els resultats obtinguts demostren el potencial d'aquests compostos i de la seva combinació com a estratègia terapèutica per al neuroblastoma
Estudi de les vies de transducció de senyals que regulen l'expressió gènica de la isoforma hepàtica de la 6-fosfofructo-2-quinasa/fructosa-2,6-bisfosfatasa per insulina by Elisabet de los Pinos Pont( Book )

2 editions published between 2000 and 2001 in Catalan and held by 2 WorldCat member libraries worldwide

Purificació i caracterizació dels isoenzims de la 2,3-bisfosfoglicerat sintasa-fosfatosa de teixits de porc by Albert Tauler Girona( )

1 edition published in 1985 in Catalan and held by 2 WorldCat member libraries worldwide

Anàlisi in silico de malalties: des de les mutacions fins les xarxes biològiques by Eduard Porta Pardo( Book )

2 editions published between 2012 and 2013 in Multiple languages and English and held by 2 WorldCat member libraries worldwide

In the era of "omics" data, the use of computational approaches to store, integrate and analyze biological information is becoming a priority, particularly in the field of biomedicine and the study of diseases. Bioinformatics methods have been successfully applied to numerous problems derived from this data explosion, such as the integration of experimentally-derived raw data with other sources of biological information in order to analyze it, the identification of features specific for biologically relevant sets of genes (such as those related to disease) or the prioritization of long lists of genes and mutations potentially associated to different phenotypes. In this thesis we will develop a new relational database of genes and mutations associated to disorders where annotations will be mapped to ontologies. By doing so, we will overcome some limitations of existing databases, such as their lack of normalization of annotations. This will provide us an optimal framework to investigate the use of ontologies and enrichment analysis to identify disease-specific mutation features that, hopefully, will help us in understanding some aspects of the underlying molecular biology of these diseases. Finally, we will explore whether networks derived from different types are better are predicting different diseases. Moreover, we will also test several combinations of these networks in order to see if they perform better than the networks alone
Control de l'expressió del gen de la 6-fosfofructo-2-quinasa/fructosa-2,6-bisfosfatasa per diferents factors de creixement en fibroblasts Rat-1 by Cristina Salvadó i Morelló( Book )

2 editions published between 1995 and 1996 in Catalan and held by 2 WorldCat member libraries worldwide

Purificación y caracterización de las isoenzimas de la 2,3-bisfosfoglicerato sintasa-fosfatasa de tejido de cerdo by Albert Tauler Girona( Book )

3 editions published in 1985 in Spanish and held by 2 WorldCat member libraries worldwide

Predicción de respuesta a tratamiento en pacientes con carcinoma escamoso de cabeza y cuello by Miguel Ángel Pavón Ribas( Book )

2 editions published in 2009 in Spanish and held by 2 WorldCat member libraries worldwide

Regulation of E2F1 transcription factor by glycogen synthase Kinase-3-Beta by Gisela Garcia Alvarez( Book )

2 editions published in 2005 in English and held by 2 WorldCat member libraries worldwide

Estudio de las propiedades conformacionales de las proteínas mediante el uso de modelos de baja resolución basados en la discretización de las coordenadas internas by Francisco Martin Bandera( Book )

2 editions published in 2018 in Spanish and held by 2 WorldCat member libraries worldwide

El campo que estudia las propiedades y comportamiento de las proteínas así como las interacciones entre ellas es tan complejo que a día de hoy resulta complicada su caracterización en detalle, sea utilizando herramientas experimentales o mediante análisis de modelización, como la homología o las técnicas ‘ab initio'. Debido a su importancia en las funciones biológicas y el amplio rango de actividades que desempeñan las proteínas, resulta indispensable la creación y utilización de nuevos modelos/programas que sirvan como herramientas eficaces para su estudio. Esto ha hecho que se haya desarrollado una serie de modelos de baja resolución que permiten realizar simulaciones cuando no es necesario un gran detalle estructural pero se requieren tiempos de simulación elevados. En el presente trabajo hemos desarrollado un modelo propio y hemos explorado su viabilidad en dos casos de relevancia biológica. El objetivo principal de este trabajo ha sido el desarrollo de un programa versátil que pueda utilizarse en diferentes tipos de estudios; se basa en un modelo simplificado de la estructura de la proteína que utiliza únicamente los carbonos alfa de la proteína y discretiza su espacio conformacional. Las aplicaciones constituyen el segundo objetivo de este trabajo, y van encaminadas a valorar la aplicabilidad del programa. En un primer estudio hemos desarrollado un protocolo específico para el estudio de las mutaciones de las regiones de baja complejidad en las proteínas (LCRs), y extraemos conclusiones biológicamente relevantes sobre la patogenicidad de sus mutaciones. En el segundo estudio hemos obtenido un bloque de resultados donde hemos analizado el efecto del volumen excluido sobre las correlaciones entre residuos. Esto nos ha permitido identificar la existencia de un efecto no biológico en el que las correlaciones aumentan cuando mayor es la distancia geométrica entre los residuos
The Multiple Tasks Endured by PI3K during neural tube development by Mª Blanca Torroba Balmori( Book )

2 editions published between 2016 and 2017 in English and held by 2 WorldCat member libraries worldwide

Development of the spinal cord involves coordination between exposure to localized extracellular signals and controlled activation of intracellular signaling pathways. This way, neuroepithelial cells firstly proliferate apically to increase the progenitor pool and, later on, initiate neurogenic divisions giving rise to a variety of neuronal cell types. Class IA PI3Ks are heterodimeric enzymes (catalytic+regulatory subunits) activated by receptors tyrosine kinase (RTKs) or G protein coupled receptors (GPCRs) that, upon extracellular stimuli, modulate diverse target proteins through local production of PtdIns(3,4,5)P3 lipids. Vertebrates express three Class IA catalytic subunits (p110-alpha, p110-beta, and p110-delta), all important for the development of the central nervous system. However, it is unclear to what extent these p110-alpha isoforms have overlapping or distinct biological roles, and what exact functions they hold in neural development. Analysis of PI3Kalpha (p110-alpha-alpha+regulatory subunit) expression in the embryonic spinal cord revealed abundant mRNA and protein levels in cycling progenitors followed by restriction of PI3K-alpha exclusively to differentiating neurons. To examine the role of PI3K-alpha in progenitors and neurons, we interfered with normal PI3K-alpha regulation by expressing active mutants or knocking down of p110-alpha-alpha in the chicken neural tube. Loss of p110-alpha resulted in high apoptotic rates in both progenitors and neurons, sustaining a role for PI3K-alpha in neural survival as seen in other studies. Instead, uncontrolled upregulation of PI3K-alpha activity resulted in severely disrupted neural tubes, with abnormal cell masses in the luminal face of the neuroepithelium and ectopic mitosis. Additionally, we observed alterations in the neural lamination characterized by basement membrane breaches followed by enhanced neural migration and misoriented axonal growth. A thorough analysis of the tissue unveiled loss of polarity as the main cellular mechanism driving the luminal structural aberrations, suggesting a major role of PI3K-alpha in neuroepithelial apico basal polarity. Moreover, the rescue of the depolarization phenotype with a dominant negative form of RhoA proposes local regulation of the Rho family of small GTPases as the molecular mechanism responsible for the PIP3 dependent regulation of adherens junction dynamics. Alternatively, we found the neural overmigration caused by excess of PI3K-alpha activity explained by increased basal accumulation of PIP3, leading to actin based membrane protrusions and basement membrane breaches. Coherently, when we assessed the neural positioning after p110-alpha knock down, we detected neurons inserted in the proliferative layer and reduction of the neuronal cytoskeletal component beta III tubulin, suggesting that PI3K-alpha also modulates morphological maturation and apico basal positioning of differentiating neurons. Interestingly, PIP3 induced overmigration seemed to be carried out through local activation of other two members of the Rho GTPases, Cdc42 and Rac1. These results shed some light upon the PI3K-alpha/PIP3 specific roles during early neural tube development, stressing out its function in cell polarity. Furthermore, we propose a mechanism that may partially explain how the PI3K-alpha /PIP3 signaling is able to control different types of polarity corresponding to different developmental moments. This could help to understand the initial events leading to some neurodevelopmental disorders caused by hyperactivation of PI3K signaling
Cambios en la expresión génica inducidos por la mitramicinas by Carolina Vizcaíno Sarmiento Pérez( Book )

2 editions published in 2014 in Spanish and held by 2 WorldCat member libraries worldwide

En esta tesis doctoral se ha examinado la interferencia de fármacos que se unen al DNA con la interacción de factores de transcripción en los promotores de genes sobre-expresados en algunos tipos de cáncer. El tratamiento de células humanas HCT116 de carcinoma de colon y A2780 de carcinoma de ovario con concentraciones nanomolares sub-letales de dos nuevos análogos de la Mitramicina A: Mitramicina SK (MSK) y demicarosil-3-D-[beta]-D-digitoxosil-Mitramicina SK (DIG-MSK), produjo cambios en los perfiles de expresión génica que se relacionaron con la respuesta celular. Se ha obtenido información acerca del mecanismo de acción de DIG-MSK, comparándolo con la MSK en células HCT116. DIG-MSK se comportó como un agente antiproliferativo más eficiente, en cuanto resultó (de acuerdo a su IC75) aproximadamente 2 veces más potente en inhibir el crecimiento celular, induciendo una muerte por apoptosis/apoptosis secundaria. En ambas líneas celulares, DIG-MSK moduló la expresión de un amplio número de genes, según se desprende de los análisis cuantitativos mediante qRT-PCR y microarrays. Muchos de los genes reprimidos tras el tratamiento farmacológico están implicados en la progresión tumoral y participan en procesos biológicos y funciones moleculares relacionadas con transcripción y su regulación celular, incluyendo la actividad de factores de transcripción. El factor de transcripción Sp1, activó la mayoría de los genes reprimidos por los fármacos y participó también en el aumento de la regulación de algunos genes principalmente relacionados con la respuesta a condiciones de estrés, entre ellos p21WAF1/CDKN1A implicado en la parada de las células en los puntos de control G1 y G2/M. El control de la expresión génica por otros factores de transcripción (CREB, E2F y EGR1) que, al igual que Sp1, reconocen regiones ricas en C/G en promotores, también se alteró tras el tratamiento con los nuevos análogos de la Mitramicina A. Los cambios en la distribución del ciclo celular y los niveles proteicos después de los tratamientos con cada fármaco fueron consistentes con los cambios observados en la expresión génica. La influencia de DIG-MSK sobre la transcripción génica en las líneas tumorales evaluadas junto a su perfil farmacológico mejorado, nos provee de una "proof-of-concept" que puede facilitar su entrada en pruebas pre-clínicas para el tratamiento de los cánceres de colon y ovario
The effect of inhibition od nucleotide synthesis on ribosome biogenesis and the induction of p53 by Ferran Riaño Canalias( Book )

2 editions published in 2017 in English and held by 2 WorldCat member libraries worldwide

Ribosome biogenesis is one of the most energy consuming anabolic processes in a cell, required for the generation of the translational machinery to grow and proliferate. Moreover, this process necessitates the coordination of protein and nucleotide synthesis to generate ribosomal proteins (RPs) and ribosomal RNA (rRNA). Critically, increased rates of ribosome biogenesis are a hallmark of c-Myc driven CRC required to sustain exacerbated growth and proliferation, with recent studies showing that drugs that target ribosome biogenesis are clinically efficacious. We have previously shown that upon ribosome biogenesis impairment, a pre‐ribosomal complex formed by RPL11 and RPL5 and noncoding 5S rRNA is re‐directed from the incorporation into the pre-60S ribosome, to bind and inhibit HDM2, leading to p53 stabilization and cell cycle arrest. We have termed this response the Impaired Ribosome Biogenesis Checkpoint (IRBC). In this study I set out to analyze the effect of nucleotide depletion on ribosome biogenesis in c-Myc-driven CRC cell lines, addressing the role of the IRBC. Nucleotide depletion inhibited rRNA synthesis and elicited the IRBC, p53 stabilization, but failed to induce G1 cell cycle arrest as previously reported. I found that this was due to the loss of 5S RNA production, the limiting factor in triggering the IRBC, causing a disruption of the IRBC complex. Moreover, this allowed cells to escape G1 arrest and enter S phase, where they encountered replicative stress. These data support the hypothesis that in nucleotide deprived conditions the IRBC acts to hold cells in G1 to prevent them from replicating their DNA cells and eventually encountering genomic instability
Study of the molecular mechanisms responsible for E2F1-induced Mtorc1 activation by Nathalie Meo Evoli( Book )

2 editions published in 2014 in English and held by 2 WorldCat member libraries worldwide

The oncogenic properties of E2F1 have been traditionally associated with the role of the oncogene in proliferation, but during the last few years many other functions associated with this family of transcription factors have been emerging. We focused on the study of the oncogenic properties of E2F1 not related to the cell cycle progression. In particular, previous results of our research group demonstrated that the overexpression of mammal E2F1 induces cellular growth by activating the mTORC1 pathway. Taking into account the well known implication of the mTOR pathway in cancer, the general aim of the Thesis is to elucidate the molecular mechanism by which E2F1 regulates mTORC1. This led us to novel observations concerning the ability of E2F1 in regulating V-ATPase activity, intracellular trafficking and autophagy repression. Specifically, we demonstrated that E2F1 enhances the activity of V-ATPase, the major regulator of lysosomal pH. By modulating this activity, E2F1 is capable of regulating lysosomal biology. This leads to the activation of mTORC1, to the relocalization of lysosomes to the cell periphery and to the repression of the autophagy flux. We showed that, similarly to the amino acids signaling, E2F1 activation pro- motes the translocation of mTOR to lysosomes and also induces an increase in the binding of mTORC1 to the lysosomal protein RagB. Our immunofluorescence analysis revealed that mTORC1 activity is not necessary for the peripheral movement of lysosomes regulated by E2F1. However, the depletion of Raptor totally abrogates this response. The ability of E2F1 to act as an autophagy repressor is due to its capacity in driving lysosomes to cell periphery and also in activating mTORC1. Moreover, we identified kinesin KIF2A as a novel transcriptional target of E2F1. Although KIF2A basal levels are required for E2F1-induced mTORC1 activation, the increase in KIF2A levels triggered by E2F1 does not contribute to mTORC1 activation. E2F1 enhances V-ATPase activity, and this modulation is required for E2F1-induced lysosomal trafficking and mTORC1 activation. E2F1 promotes an increase in the binding of the C1 subunit of the V1 domain, ATP6V1C1, to the V-ATPase/RagB lysosomal complex, suggesting that such binding could be the mechanism through which E2F1 enhances V-ATPase activity. Finally, we showed that E2F1 activation leads to a general re-arrangement of the cytoskeleton and that, moreover, is required to promote cell migration. Several studies indicated a high correlation between E2F1 overexpression and metastasis. Our data showing that E2F1 is required for cell migration are in agreement with the theory of E2F1 being a promotor of invasiveness. Taking into account the implication of V-ATPase in cancer, our novel observations concerning the ability of E2F1 to regulate the peripheral movement of lysosomes and to enhance V-ATPase activity help us to better understand the role of E2F1 in invasion and metastasis
Smad binding codes broken by WW domain containing proteins = Dexifrant els codis d'unió a Smad de les proteïnes amb dominis WW by Eric Aragón Altarriba( Book )

2 editions published between 2013 and 2014 in English and held by 2 WorldCat member libraries worldwide

Cell fate is controlled by a multitude of signals and loss of this control has devastating consequences for living organisms. One of the key players in this network of signals is the TGF-beta family of cytokines. These hormones trigger an immense amount of responses by sending activated Smad transcription factors (Sma and Mad related proteins) to the nucleus where participate in the control of stem cell pluripotency and differentiation, embryo development, tissue regeneration, and differentiated tissue homeostasis (Massagué, 1998). According to their function, Smad proteins are classified as receptor regulated Smads (R-Smads), which include Smads 1, 5 and 8 in the BMP-driven version of the SMAD pathway, and Smads 2 and 3 in the TGF-beta/ Nodal/Activin pathways. R-Smads form complexes with the common co-activator Smad (Co-Smad) Smad4. The SMAD family also contains the two inhibitory Smads (I-Smads), Smad6 and Smad7, which provide critical negative regulation to these powerful and ubiquitous pathways. All Smad proteins are modular (Shi and Massagué, 2003). R-Smads and the Co-Smad consist of two Mad Homology MH1 and MH2 domains connected by a linker that functions as a scaffold upon which other proteins can interact and modulate the functional outcome. This linker contains a conserved cluster of phosphorylation sites adjacent to a PY motif. MH1 domains of R-Smads and Smad4 bind to DNA, whereas the MH2 domain and the linker function as scaffolds for receptors, regulator proteins, and transcription cofactors to interact and determine the outcome of the signal (Shi and Massagué, 2003). Compared to R-Smads and Co-Smads, the I-Smads have low sequence similarity in the MH1 domain but conserve an MH2 domain and a linker region with a characteristic PY motif. The presence of the common regions facilitates the competition of R-Smads and I-Smads for the receptor and ligands and it facilitates the inhibitory role of I-Smads (Figure 1). I-Smads are expressed in response to TGF-[beta] or BMPs to provide negative feedback in the pathway (Bai and Cao, 2002; Hata et al., 1998; He et al., 2002; Kavsak et al., 2000; Nakao et al., 1997; Yan and Chen, 2011) and in response to other pathways such as STAT to oppose TGF-[beta] signaling (Ulloa et al., 1999). Smad6 interferes with the formation of Smad1-Smad4 complexes (Hata et al., 1998) whereas Smad7 interferes with the formation of R-Smads-Smad4 complexes and inhibits TGF-[beta] and BMP receptors (Hayashi et al., 1997; Topper et al., 1998). Several key phosphorylations drive the Smad signaling process. The ligand cytokines activate receptor serine/threonine protein kinases that phosphorylate Smad proteins at the C-terminus. The BMP receptors act on Smads 1, 5 and 8 and the receptors for the TGF-beta /nodal/activin/myostatin group of ligands act mainly on Smads 2 and 3 (Shi and Massagué, 2003). The phosphorylated C-terminus provides a binding site for Smad4, which is an essential component in the assembly of target-specific transcriptional complexes. These phosphorylations are reversed by protein phosphatases that limit the general pool of activated Smad molecules (Inman et al., 2002; Lin et al., 2006; Schmierer et al., 2008; Xu et al., 2002)
Role of the Tousled like kinases in maintaining genome and epigenome stability by Sandra Segura Bayona( )

2 editions published in 2018 in English and held by 2 WorldCat member libraries worldwide

Histone deposition during DNA replication, transcription and repair ensures the faithful maintenance of genetic and epigenetic information. The histone H3-H4 chaperone ASF1 participates in both replication dependent and independent nucleosome assembly. While much attention has been focused on the role of histone modifications, the significance of histone chaperones and their regulation in chromatin maintenance remains relatively unexplored. The Tousled like kinases 1 and 2 (TLK1 and TLK2) are evolutionarily conserved Ser/Thr kinases that regulate ASF1. TLKs have been implicated in DNA repair and chromosome stability but their cellular functions remain poorly defined. Apart from ASF1, the DNA damage signaling protein RAD9 is another proposed target of TLK activity but the extent to which they both rely on TLK1/2 has not been clearly established. The goal of this thesis is to characterize the relative functions of TLK1 and TLK2, identify their cellular targets, modes of regulation and consequences of their deficiency during development and in cancer. To this end, we have generated conditional mouse models with loss of function alleles, studied mouse-derived cells from homeostatic and cancerous tissues, and performed siRNA mediated depletion of TLK1/2 in multiple human cell lines. In vivo, TLK1 and TLK2 play largely redundant roles in genome maintenance and cell viability in tissue homeostasis, with the exception of a placental specific requirement for TLK2. Depletion of TLK activity in cells leads to reduced histone deposition, DNA replication stress, extensive DNA damage accumulation and arrest or cell death. In addition, TLK deficient cells exhibit synthetic lethality with several DNA damage checkpoint inhibitors, consistent with a role for TLK activity in replication stress tolerance. Genome wide analysis indicated that TLK activity is required for heterochromatin maintenance, particularly in regions of repetitive DNA. This is consistent with defects in histone variant deposition and increased non-coding RNA transcription at these sites. While the phenotypes of TLK depletion support a major role in ASF1-mediated histone deposition, our data indicates that they likely control additional targets and suggests that the identification of small molecule inhibitors for these kinases could suppose a valuable target for cancer therapy to augment existing strategies for cancer treatment
Prions i agregons com a inhibidors de start : una via a l'envelliment cel·lular by David Moreno Fortuño( Book )

2 editions published in 2017 in Catalan and held by 2 WorldCat member libraries worldwide

"Saccharomyces cerevisiae és un model escaient per estudiar el procés d'envelliment a nivell cel.lular gràcies al seu mecanisme de divisió asimètrica. Fent una analogia amb l'envelliment en organismes superiors, on les cèl.lules somàtiques són pròpies de l'individu i envelleixen amb ell, mentre que les cèl.lules de la línia germinal són capaces de formar un nou individu i són virtualment immortals en la població, en S. cerevisiae podem diferenciar dos tipus de cèl.lules: les cèl.lules mare, que envelleixen i poden produir unes 20-30 cèl.lules filles, i les cèl.lules filles, que són capaces d'esdevenir mares i tornar a fer 20-30 cèl.lules filles més independentment de l'edat de la seva mare en el moment de néixer, excepte si la mare ja és molt vella. Per tant, en estudiar l'envelliment de les cèl.lules mare del llevat de gemmació podem aprendre molts dels mecanismes que condueixen l'envelliment cel.lular, especialment a nivell molecular. Entre les característiques que adquireixen les cèl.lules mare de llevat durant el procés d'envelliment, l'acumulació de dipòsits proteics insolubles, proteïnes carbonilades i agregats proteotòxics sembla jugar un paper molt important. Donada la seva preponderància també en organismes superiors, juntament amb les afectacions mitocondrials, ens interessava entendre la relació entre la presència d'aquests dipòsits proteotòxics i la maquinària de cicle cel.lular, especialment durant G1 sobre la Xarxa de Start. Sabem que les xaperones tenen un paper clau en Start per a executar l'entrada en el cicle cel.lular i, en ser segrestades per els agregats proteotòxics en cèl.lules envellides podrien ser causa directa de senescència replicativa. Per tal de comprovar aquesta hipòtesi, en primer lloc hem constatat que els agregats proteotòxics endarrereixen la progressió durant G1, aboleixen la coordinació entre velocitat de creixement i la mida crítica de Start, i redueixen fortament la longevitat de les cèl.lules del llevat. D'altra banda, mitjançant diferents aproximacions que permeten l'estudi de l'envelliment de les cèl.lules mare del llevat (algunes de les quals desenvolupades en aquest treball), hem observat que en els últims cicles de cèl.lules envellides es produeix un clar retard en la progressió durant G1, així com que la majoria de cèl.lules moren estant en aquesta fase del cicle cel.lular, quan en les cèl.lules mare joves aquesta fase és la més curta. Especialment rellevant en el nostre estudi, hem demostrat que el grau de disponibilitat de xaperones disminueix clarament en cèl.lules velles. Finalment, veiem que la superexpressió de l'activador del cicle cel.lular Cln3 allarga la longevitat de les cèl.lules, fins i tot si aquesta activació es fa sobre cèl.lules parcialment envellides prèviament com si ho fem sobre mutants d'algunes xaperones clau per a l'activació del cicle cel.lular. En resum, com a resultat de l'acumulació d'agregats proteotòxics en cèl.lules envellides, la pèrdua d'activitat xaperona arribaria a comprometre l'entrada en el cicle cel.lular i, així, podria explicar la pèrdua de capacitat proliferativa que té lloc durant el procés d'envelliment cel.lular." -- TDX
Efecte de l'HGF i del TGF-[beta] sobre l'expressió de la 6-fosfofructo-2-quinasa/fructosa-2,6-bisfosfatasa a cultiu primari d'hepatòcits by Manel Joaquin i Caudet( Book )

3 editions published between 1997 and 1998 in Catalan and held by 2 WorldCat member libraries worldwide

The Role of GCP8 in microtubule nucleation and cell proliferation by Artur Ezquerra González( Book )

2 editions published in 2019 in English and held by 2 WorldCat member libraries worldwide

Connecting centrosomes, cilia and the DNA damage response by Berta Terré Torras( Book )

2 editions published between 2016 and 2017 in English and held by 2 WorldCat member libraries worldwide

The suppression of genome instability by the DNA damage response (01R) is critical for preventing human diseases characterized by developmental defects, infertility and in some cases, elevated cancer predisposition. After DNA damage, the activation of the related ATM and ATR kinases is crucial to amplify a signal transduction cascade required for the proper cellular responses to ensure genomic integrity. Mutations in ATR and other genes involved in the 01R have been identified in patients with Seckel syndrome, that is characterized by microcephaly and dwarfism. As defects in many centrosomal proteins also underlie Seckel Syndrome, it has been suggested that a crosstalk between the 01R and centrosome may be important. Supporting this idea, several MCPH/Seckel proteins, such as MCPH1, CEP152, and CEP63 have been implicated in both centrosomal and 01R functions and many DNA repair factors have been identified at the centrosome. In this thesis, we describe the in vivo functional characterization of two proteins implicated in the 01R, CEP63 and GEMC1. We found that they both have distinct critical roles in preventing multisystem pathology in mice. CEP63 is a centrosome protein that facilitates centriole duplication through the recruitment of CEP152 in the centrosome and has been implicated in the 01R as an ATR/ATM target gene in Xenopus. Human CEP63 mutations cause Seckel syndrome, characterized by growth retardation, microcephaly and mental retardation, although the pathological outcomes are milder than those associated with mutations in ATR. In mice, deficiency in Cep63 leads to microcephaly due to the attrition of neural progenitor cells. Using genetic analysis, we showed that this was through a p53-mediated cell death pathway triggered by centrosome-based mitotic errors and independent of the ATM and CHK2 kinases, that activate p53 after DNA damage. GEMC1, a protein that belongs to the Geminin superfamily together with MCIDAS, was originally identified in Xenopus as a pro-replication factor. The characterization of mice lacking GEMC1 revealed its crucial role in regulating two differentiation programs in mammals, multiciliogenesis and spermatogenesis. Gemc1-deficient mice are growth impaired, develop hydrocephaly and are infertile due to defects in the formation of multiciliated epithelial cells in the brain, respiratory tract, oviducts and efferent ducts of the epididymis. We demonstrated that GEMC1 acts at the top of the transcriptional cascade that drives multiciliogenesis and, like MCIDAS, it controls transcription through the association with E2F4/5 and the cofactor DP1. In addition, we found that Gemc1-deficient mice are infertile due to defects in the terminal differentiation of spermatozoa, a process known as spermiogenesis. Although no patients harboring GEMC1 mutations have been identified to date, we believe that Gemc1 is a good candidate for the rare mucociliary clearance disorder referred as Reduced Generation of Multiple Motile Cilia (RGMC) cauterized by defects in multiciliated cell development. To date, mutations in only two genes have been implicated in RGMC in humans, MCIDAS and CCNO. Thus, the generation of these animal models has provided new insights into the molecular functions of CEP63 and GEMC1 in many tissues and expanded our knowledge of the etiology of pathologies associated with rare human diseases
 
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Alternative Names
Albert Tauler wetenschapper

Tauler Girona, Alberto

Tauler i Girona, Albert

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