Дисертації з теми "HnRNPA1"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-50 дисертацій для дослідження на тему "HnRNPA1".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте дисертації для різних дисциплін та оформлюйте правильно вашу бібліографію.
Najim, Mustafa. "Hepatitis C virus induced changes in cellular trafficking and lipid metabolism - identifying novel host factors required for HCV replication." Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/20895.
Повний текст джерелаLabrecque, Benoît. "Identification des résidus contribuant à l'interaction hnRNP A1- hnRNP A1." Mémoire, Université de Sherbrooke, 2003. http://savoirs.usherbrooke.ca/handle/11143/3336.
Повний текст джерелаFisette, Jean-François. "Le contrôle de l'épissage alternatif par les protéines hnRNP H et hnRNP A1." Thèse, Université de Sherbrooke, 2009. http://savoirs.usherbrooke.ca/handle/11143/4275.
Повний текст джерелаMoran-Jones, Kim. "hnRNPs A2 and A3 : nucleic acid interactions /." St. Lucia, Qld, 2004. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17983.pdf.
Повний текст джерелаJansen, Lara [Verfasser], and Christian [Akademischer Betreuer] Haass. "Generation and functional analysis of the ALS associated HNRNPA zebrafish mutants / Lara Jansen ; Betreuer: Christian Haass." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/122243654X/34.
Повний текст джерелаBarral, Paola. "Characterization of a novel hnRNP : E1B-AP5." Thesis, University of Birmingham, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.403905.
Повний текст джерелаLe, Bras Morgane. "Rôle des protéines de liaison à l'ARN hnRNP H et hnRNP F dans les régulations traductionnelles dans les glioblastomes." Thesis, Toulouse 3, 2018. http://www.theses.fr/2018TOU30277.
Повний текст джерелаGlioblastoma multiforme (GBM) is one of the most aggressive brain tumors with poor prognosis. Understanding the molecular mechanisms involved in the development and resistance to treatments of gliomas could improve treatment efficiency. Recently, it has been demonstrated that translational regulations play a key role in the GBM aggressivity. RNA binding proteins (RBP) are major regulators of these processes and have altered expression / activity in GBM. The RBP hnRNP H and hnRNP F (HF) are among the most overexpressed RBP in GBM and their role in GBM translational regulation has never been investigated yet. We hypothesize that HF are at the core of a post-transcriptional regulation network which impacts the translational machinery that controls GBM tumor development and resistance to treatment. We have demonstrated that hnRNP H and hnRNP F regulate proliferation and response to treatment because their depletion (i) decreases the GBM proliferation (cell line model, spheroid and in vivo xenografts), (ii) activates the DNA damage response pathways and (iii) sensitizes the GBM cells to irradiation. We have identified HF as new regulators of GBM translation. Indeed, our data show that hnRNP H and hnRNP F control mRNA translation by regulating expression/activity of initiation factors and in collaboration with RNA helicases by targeting mRNA involved in oncogenic processes and containing secondary structures called G-quadruplex in their 5'UTR. The data that we have generated suggest that HF are essential translational regulators involved in tumor development and resistance to treatment in GBM
Santerre, Maryline. "Étude de l'action sur l'épissage de protéines nucléaires se liant à la région de l'ARN du virus VIH-1 contenant le site d'épissage A7 et role de ces protéines sur d'autres sites accepteurs d'épissage de VIH-1." Thesis, Nancy 1, 2010. http://www.theses.fr/2010NAN10115/document.
Повний текст джерелаHIV-1 pre-mRNA splicing depends upon 4 donor and 8 acceptor sites, which are used in combination to produce more than 40 different mRNAs. To further characterize nuclear factors involved in these processes, we purified RNP complexes formed by incubation of SLS2-A7 transcripts in HeLa cell nuclear extracts by affinity chromatography to identify new associated proteins. We showed that, in addition to the well known hnRNP A1 inhibitor of site A7, nucleolin, hnRNP H and hnRNP K interact directly with SLS2-A7 RNA. We demonstrated that hnRNP K has multiple binding sites in the vicinity of site A7 and that binds cooperatively to hnRNP A1 to the A7 RNA region and limits the A7 utilization in vitro. As hnRNP A1 is a negative regulator of several HIV-1 splicing sites (A1, A2, A3), we tested whether hnRNP K may also reinforce hnRNP A1 inhibition at these sites. Surprisingly, hnRNP K activated in vitro splicing of the D1-A1, D1-A2 and D1-A3 introns. Interestingly, hnRNP K was found to reinforce strongly the ASF/SF2 activity at site A2, which indicates that depending on the splicing site hnRNP K can be a splicing activator or inhibitor. To test how hnRNP K influences the relative utilization of HIV-1 splicing sites in cellulo, we used plasmid p PSP containing all the HIV-1 splicing sites and tested the effect of over-expression in HeLa cells on alternative splicing of the PSP RNA. Doubling the amount of hnRNP K in HeLa cells led to a drastic change of the PSP RNA alternative splicing, which confirms the strong influence of hnRNP K on alternative splicing. Moreover, increase of cellular concentration of hnRNP K strongly decrease the viral Nef protein production. hnRNP K protein affects A7 splicing regulation but also regulates the majority of regulated splicing sites of HIV. By extension of the study of hnRNP K effect to other HIV-1 splicing sites, we discovered that hnRNP K is a general regulator of HIV-1 splicing
Paradis, Caroline. "Rôles de SRp30c et hnRNP I/PTB dans le contrôle de l'épissage alternatif du pré-ARN messager de hnRNP A1." Mémoire, Université de Sherbrooke, 2007. http://savoirs.usherbrooke.ca/handle/11143/3857.
Повний текст джерелаSöderberg, Malin. "Post-Transcriptional Regulation of the Murine Inducible Nitric Oxide Synthase Gene." Doctoral thesis, Uppsala University, Department of Pharmaceutical Biosciences, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6137.
Повний текст джерелаLarge amounts of nitric oxide (NO) are produced by the inducible nitric oxide synthase (iNOS) upon inflammatory stimuli. NO is a multifaceted molecule, which may have beneficial effects as an antimicrobial agent in the immune defense, or cytotoxic effects in chronic inflammations, manifested as e.g. arthritis and asthma. Understanding the mode of regulation of the iNOS gene is a prerequisite for developing intervention strategies in various pathological conditions where detrimental effects of NO need to be prevented.
Transcriptional processes of the iNOS gene regulation are well described, while post-transcriptional events have not been studied in detail. The aim of the present thesis was to investigate post-transcriptional regulatory mechanisms involving the 3’untranslated region (UTR) of the murine iNOS mRNA.
Inflammation-dependent RNA-protein interactions with the iNOS mRNA 3’UTR were characterized by RNA gel shift analysis and UV cross-linking. Trans-acting factors interacting with the 3’UTR were detected in mouse liver and macrophages and identified as heterogeneous nuclear ribonucleoproteins (hnRNP) I and L. Western blot revealed that reduced hnRNPI levels are responsible for the decreased interaction of hnRNPI with iNOS 3’UTR upon induction in inflammatory conditions. This decrease was reversed by the glucocorticoid dexamethasone, concomitant with decreased iNOS mRNA levels and stability. Introduction of the iNOS 3’UTR into a luciferase reporter gene reduced its expression in macrophages. Upon deletions of the binding sites for hnRNPI and hnRNPL, the luciferase expression was recovered. In addition, inflammatory stimuli increased the luciferase activity of the construct with the full-length 3’UTR, while only weak effects of the stimuli were seen on the deletion constructs.
In conclusion, the results suggest that binding of hnRNPI and hnRNPL to the iNOS mRNA 3’UTR promotes degradation of the transcript. Induction of iNOS by inflammatory stimuli dissociates the RNA-protein complex, yielding a more stable mRNA. In addition, post-transcriptional down-regulation of the iNOS gene by the anti-inflammatory glucocorticoid dexamethasone, seems to involve hnRNPI.
Christian, Kyle. "The role of hnRNP A1 and hnRNP C1/C2 in the regulation of the stress responsive genes Cyp2a5/2A6 and p53." Doctoral thesis, Uppsala University, Department of Pharmaceutical Biosciences, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8722.
Повний текст джерелаThe family of proteins known as heterogeneous nuclear ribonucleoproteins (hnRNPs) is large and diverse. Often, one and the same hnRNP will perform multiple cellular functions, leading to their description as “multifunctional proteins”. The two hnRNPs known as hnRNP A1 and hnRNP C1/C2 are multifunctional proteins found to affect the transcription, splicing, stability, and translation of specific genes’ mRNA. They are implicated in carcinogenesis, apoptosis, and DNA damage response mechanisms.
The aims of this thesis were to study the hnRNP A1 and hnRNP C1/C2 dependent regulation of two highly stress responsive genes, the tumor suppressor p53 and the cytochrome P450 enzyme Cyp2a5/CYP2A6. We identified hnRNP C1/C2 as a DNA damage induced binding protein towards the coding region of p53 mRNA, and found that while a specific cis binding site appears to have a positive function in p53 expression, interaction of hnRNP C1/C2 with this site represses the expression. The data suggest that two distinct molecular mechanisms exist for the down-regulation of p53 by hnRNP C1/C2. One mechanism, active during transcriptional stress, is dependent upon the aforementioned site, and the other, independent. We discuss how hnRNP C1/C2 dependent repression of p53 may play a role in apoptosis.
The data presented here further suggest that the transcriptional and post-transcriptional processes controlling the expression of the murine Cyp2a5 gene are linked via hnRNP A1, by performing functions in the nucleus as a transcription factor, or in the cytoplasmic compartment as a trans factor bound to the 3’UTR of the mRNA as needed. Our studies of the human ortholog of this gene, CYP2A6, suggest that this gene is regulated post-transcriptionally in a manner similar to that of its murine counterpart, via changes in mRNA stability and interaction of hnRNP A1 with its 3’ UTR.
Price, Robert Jordan. "The role of histone variants and hnRNPs in early Xenopus laevis development." Thesis, University of Portsmouth, 2011. https://researchportal.port.ac.uk/portal/en/theses/the-role-of-histone-variants-and-hnrnps-in-early-xenopus-laevis-development(a938531c-ccba-4dfe-ba77-b8144278de30).html.
Повний текст джерелаPeebles, Katherine Anne. "HnRNP A2/B1 expression in neoplastic mouse lung cells /." Connect to full text via ProQuest. IP filtered, 2005.
Знайти повний текст джерелаTypescript. Includes bibliographical references (leaves 153-171). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;
Lodge, Anthony Paul. "Identification of a novel protein related to HnRNP-U." Thesis, University of Liverpool, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243247.
Повний текст джерелаCordeau, Mélanie. "Implication de hnRNP A1 dans l'épissage des longs introns." Mémoire, Université de Sherbrooke, 2002. http://savoirs.usherbrooke.ca/handle/11143/3260.
Повний текст джерелаCordeau, Mélanie. "Implication de hnRNP A1 dans l'épissage des longs introns." [S.l. : s.n.], 2002.
Знайти повний текст джерелаShan, Jianguo. "The role of hnrnps in a2re-mediated rna trafficking in oligodendrocytes and neurons /." [St. Lucia, Qld.], 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16858.pdf.
Повний текст джерелаLandsberg, Michael. "Structural studies on the cytoplasmic RNA transport factor, hnRNP A2 /." St. Lucia, Qld, 2003. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17441.pdf.
Повний текст джерелаSeraj, Z. I. "Core proteins of rat liver heterogeneous nuclear ribonucleoprotein (hnRNP) particles." Thesis, University of Glasgow, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.380388.
Повний текст джерелаQuaresma, Alexandre Jose Christino. "Estudos funcionais e estruturais da proteina humana hnRNP Q/NSAP1." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314763.
Повний текст джерелаTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-11T07:55:23Z (GMT). No. of bitstreams: 1 Quaresma_AlexandreJoseChristino_D.pdf: 9068041 bytes, checksum: 9661a43a5c28440721d55ca90f6c94ac (MD5) Previous issue date: 2008
Resumo: Os membros da família de proteínas chamada hnRNPs (heterogenous nuclear ribonuclein proteins) apresentam importantes papeis no controle da expressão gênica e no metabolismo dos mRNAs. Os membros hnRNPD (AUF1) e hnRNPQ (NSAP1) foram alvos deste estudo. AUF1 apresenta dois domínios de ligação à RNA do tipo RRM (RNA recognition motif) e participa ativamente no processo de desestabilização de uma classe de mRNAs que apresentam um motivo rico em AU na região 3' não traduzida. Demonstramos, através do sistema de duplo híbrido em levedura, que a isoforma p37 de AUF1 interagiu com as proteínas hnRNPQ, IMP-2, NSEP1 (YB-1) e UBC9. Além disso, a proteína hnRNPQ também foi pescada num outro ensaio de duplo híbrido em levedura, que utilizou como isca a proteína humana arginina metiltransferase (PRMT1). hnRNPQ apresenta, na sua região Cterminal, um ¿motivo rico em argininas e glicinas¿ (RGG box). Demonstramos que ela é alvo de metilação pela PRMT1 in vitro e in vivo. Funcionalmente, sua metilação é importante para sua localização nuclear. NSAP1 têm uma constituição modular com um domínio ácido (AcD) no seu Nterminal, seguido por três domínios de ligação à RNA do tipo RRM e o já mencionado RGG box no seu C-terminal. Funcionalmente hnRNPQ está envolvido em vários aspectos do etabolismo de RNA, incluindo a edição do mRNA da proteína humana ApoB. Para isso, ela interage não somente com o mRNA de ApoB, mas com a enzima efetora da edição Apobec1 e com a proteína que ativadora do Apobec1 (ACF1). Mostramos que o domínio ácido, de NSAP1 é capaz de interagir com Apobec1 e que sua fosforilação in vitro pela PKC inibe esta interação. Ainda identificamos que hnRNPQ interage com proteínas da família heat shock (incluindo HSP70 e BiP), e vimos que hnRNPQ é um alvo de fosforilação principalmente pela PKCd, in vitro. A localização sub-celular de hnRNPQ é modificada pela ativação in vivo das PKCs. Em conseqüência desta ativação ou da aplicação de estresse oxidativo, térmico ou indução de estresse do reticulo endoplasmático (tratamento com tapsigargina) hnRNPQ se desloca do núcleo para o citoplasma aonde se encontra em vesículas/corpúsculos definidas. Em resumo, nossos dados sugerem que as diversas funções da hnRNPQ relacionadas ao metabolismo de mRNAs, sofrem diferentes regulações, mediadas por modificações pós-traducionais (fosforilação e metilação), que interferem tanto na sua localização celular quanto na sua afinidade por determinados proteínas parceiras
Abstract: The members of the hnRNPs family (heterogenous nuclear ribonuclein proteins) play important roles in gene expression control and mRNAs metabolism. The proteins hnRNPD (AUF1) and hnRNPQ (NSAP1) were the main targets of this study. AUF1 has two RNA recognition motifs (RRM) and participates in the process of destabilization of a class of mRNAs that contain AU-rich sequences in their 3' untranslated regions (3'-UTR). We found, using the ¿yeast two-hybrid system¿ (Y2HS), that the isoform p37 of AUF1 (AUF1p37) interacts with the proteins: hnRNPQ, IMP-2, NSEP1 (YB-1) and UBC9. Moreover, the protein hnRNPQ was also identified as a prey protein in another Y2HS screen, which used as bait the human protein Arginine methyltransferase (PRMT1). HnRNPQ presents, in its C-terminal region, an "Arginine/Glicine-rich sequence" (RGG box). We are able to show that this RGG box is a target for methylation by PRMT1 in vitro and is methylated in vivo. Functionally, this methylation is important for its nuclear localization. hnRNPQ has a modular organization with an acid domain (AcD) in its N-terminal, followed by three RNA-binding domains (RRM) and the previously mentioned RGG box in its C-terminal. Functionally, hnRNPQ is involved in diverse aspects of RNA metabolism, including editing of the mRNA encoding the human protein ApoB. It has been shown previously to interact with the mRNA of ApoB, and also with the editing enzyme Apobec1 and the Apobec1 activation protein (ACF1). Here we show that the acid domain of hnRNPQ mediates the interaction with Apobec1 and that its in vitro phosphorylation (by PKC) inhibits this interaction. Furthermore, we found that hnRNPQ interacts with members the heat shock family of proteins (including HSP70 and BiP), and demonstrated that hnRNPQ can be in vitro phosphorylated by PKCd. Finally, we discovered that the sub-cellular localization of hnRNPQ undergoes modification after activation of PKC pathways. This also occurs after application of endoplasmic reticulum stress (using tarpsigargin), oxidative or heat stress. Under all of these conditions hnRNPQ translocated from the nucleus to the cytoplasm, where it is found at defined vesicles or granules. In summary, our data suggest that the diverse functions of hnRNPQ in the context of mRNA metabolism, may suffer specific regulations, by post-translational modifications, including phosphorylation and methylation, which modify both the proteins sub-cellular localizations as well as its affinity to interacting protein partners
Doutorado
Bioquimica
Doutor em Biologia Funcional e Molecular
Richard, Travis. "ARK5 Regulates Subcellular Localization of hnRNP A1 During Hypertonic Stress." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36212.
Повний текст джерелаCornella, Nicola. "Characterization of the hnRNP RALY in RNA transcription and metabolism." Doctoral thesis, Università degli studi di Trento, 2017. https://hdl.handle.net/11572/369300.
Повний текст джерелаCornella, Nicola. "Characterization of the hnRNP RALY in RNA transcription and metabolism." Doctoral thesis, University of Trento, 2017. http://eprints-phd.biblio.unitn.it/2625/2/Disclaimer_Cornella.pdf.
Повний текст джерелаFolci, A. C. "HNRNP K: A NEW PROTEIN IN NEURON DEVELOPMENT AND FUNCTION." Doctoral thesis, Università degli Studi di Milano, 2012. http://hdl.handle.net/2434/171964.
Повний текст джерелаCourteau, Lynn. "Regulation of hnRNP A1 Cellular Localization by Protein Kinases and its Biological Impact." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32078.
Повний текст джерелаLong, Jennifer Connie. "Identification of in vivo RNA tragets of the RNA-binding proteins Acinus and hnRNP A1." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4227.
Повний текст джерелаDupuis, Sophie. "Interaction entre la protéine HnRNP A1/UP1 et les séquences télomériques humaines." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0001/MQ40578.pdf.
Повний текст джерелаCharroux, Bernard. "Contribution à l'étude fonctionnelle de la protéine hnRNP K chez Drosophila melonogaster." Aix-Marseille 2, 1997. http://www.theses.fr/1997AIX22049.
Повний текст джерелаSchwartz, Laura Link. "HnRNP E1 Protects Chromosomal Stability Through Post-Transcriptional Regulation of Cdc27 Expression." Kent State University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=kent1445519325.
Повний текст джерелаDupuis, Sophie. "Interaction entre la protéine HnRNP A1/UP1 et les séquences télomériques humaines." Sherbrooke : Université de Sherbrooke, 1998.
Знайти повний текст джерелаBlanchette, Marco. "Modulation de l'épissage alternatif de hnRNP A1 éléments de contrôle et mécanismes d'action." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0017/NQ56990.pdf.
Повний текст джерелаPratt, Kenny Matthew. "Novel properties of hnRNP-UL1 : its possible role in the pathogenesis of ALS." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6583/.
Повний текст джерелаKanhoush, Rasha. "Etude moléculaire et biochimique des interactions de la protéine hnRNP G avec l’ARN." Paris 6, 2010. http://www.theses.fr/2010PA066054.
Повний текст джерелаBlanchette, Marco. "Modulation de l'épissage alternatif de hnRNP A1 : éléments de contrôle et mécanismes d'action." Sherbrooke : Université de Sherbrooke, 2000.
Знайти повний текст джерелаChaumet, Alexandre. "Identification de nouveaux partenaires d'Ilf3 et de NF90, deux protéines aux ARN." Paris 6, 2009. http://www.theses.fr/2009PA066385.
Повний текст джерелаGarcia, Cristiana Bernadelli. "Acúmulo da ribonucleoproteína heterogênea nuclear K em câncer de cabeça e pescoço: estudos mitocondriais." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/60/60135/tde-04062014-112939/.
Повний текст джерелаHeterogeneous nuclear ribonucleoprotein K (hnRNP K) is a protein involved in gene expression processes, which has been proposed to bind mitochondrial mRNAs. Despite it to be considered a prognostic marker in cancer, the hnRNPK role in this disease is unknown. We addressed the involvement of hnRNP K in mitochondria with emphasis on bioenergetics and identification of new potential ligands of hnRNP K. The cell lines used were from head and neck squamous cell carcinoma (HN13 and CAL 27) with RNA silencing for hnRNP K , and HEK293 cells with overexpression of hnRNP K. The effects of cellular accumulation of hnRNP K in mitochondrial electron chain carriers were assessed by the activity of mitochondrial complexes I, II and V in HN13 cells. Reduced levels of hnRNP K using RNA interference promoted a decrease in the activity of the complexes in HN13 cells, indicating the involvement of the protein in the efficiency of the electron transport in mitochondrial respiratory chain. HEK293 cells with overexpression of hnRNP K (HEK293/hnRNP K) and HN13 and CAL 27 cells with silencing and stable reduction of hnRNP K were used to determine the role of hnRNP K in mitochondrial membrane potential, ATP levels, lactate production and oxygen consumption. HEK293/hnRNP K, compared to control cells, showed higher levels of ATP, reduced mitochondrial membrane potential, lower oxygen consumption and higher production of lactate. HN13 cells with reduced hnRNP K had lower ATP levels, with lower release of lactate to the extracellular medium and higher oxygen consumption. These results suggest that accumulation of hnRNP K protein plays a role in mitochondria by changing the cellular energetic metabolism from oxidative phosphorylation to glycolysis. The strategy of co-immunoprecipitation using antibodies for hnRNP K, protein digestion with trypsin, and liquid chromatography, coupled to mass spectrometer, were used to search for new potential ligands of hnRNP K. Data analysis with software SEPro identified 57 candidate proteins binding to hnRNP K. Three proteins were validated by co-IP and Western blotting: the mitochondrial transcription factor PTCD3, YB1, and PSF. We propose that hnRNP K plays a role in the mitochondrial energetics, and probably its interaction with PTCD3 participates in this function.
Silva, Vinicius Barreto da. "Modelagem molecular, síntese e avaliação da atividade biológica de potenciais antineoplásicos com a proteína hnRNP K e culturas de células tumorais." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/60/60136/tde-24092011-000316/.
Повний текст джерелаhnRNP K protein is known for its role in the multiple processes that compose gene expression, including functions during splicing, transcription and translation, developed, mainly, by the binding of nucleotides to KH domains. Inadequate activation of hnRNP K induces the development of some types of cancer, including head and neck, breast and colorectal. In this way, hnRNP K is an attractive molecular target for antineoplastic drug design. Using in silico strategies, we have identified two organic compounds, a benzimidazole and a phenylbenzamide derivatives, able to prevent the natural binding of nucleotides to hnRNP K in vitro. Applying docking, molecular interaction fields and molecular dynamics simulations it was possible to propose that such compounds present structural characteristics capable to support intermolecular interactions inside KH3 domain binding cleft, mainly with R40 and R59 residues, which are extremely important during molecular recognition of nucleotides by hnRNP K. The benzimidazole and phenylbenzamide derivatives identified are novel lead compounds that can guide the design of new antineoplastic drugs targeting hnRNP K. Considering metabolic and toxicity predictions, the phenylbenzamide seems to be more promising than the benzimidazole derivative as a drug, once the benzimidazole presents genotoxic potential. Although both derivatives prevent the binding of nucleotides to hnRNP K, biological assays with tongue cancer cell lines revealed only a mild antitumoral activity for such compounds. Higher level of cell viability reduction, 18% at 8.4 M, was observed for the phenylbenzamide derivative. Following the similarity principle, virtual screening simulations were made intending to find novel benzimidazole and phenylbenzamide derivatives inside EXPRESS-Pick database. The search revealed 21 compounds, 5 of which were tested in vitro with hnRNP K, where 3 of them were active. Intending to optimize benzimidazole and phenylbenzamide derivatives in order to design more potent chemical entities, we have suggested in silico substituents as potential bioisosteric groups of the dioxopyrrolidine rings of hnRNP K ligands, guiding the future synthesis of novel compounds with enhanced antitumoral activity. Moreover, complementary work proposition was performed through the synthesis of benzoxazepin-purines, which also present antitumoral activity but not through hnRNP K pathway. The major limitation of such derivatives is the presence of a nitro aromatic group, which can be very toxic. 20 potential bioisosteric groups were proposed as fragment candidates to replace the nitro one in order to design novel antitumoral derivatives with reduced toxic potential.
Thompson, Peter Jeffrey. "Transcriptional silencing of endogenous retroviruses by the novel lysine methyltransferase co-repressor hnRNP K." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/55760.
Повний текст джерелаMedicine, Faculty of
Medical Genetics, Department of
Graduate
Silva, Vinicius Barreto da. "Estudos de modelagem molecular e relação estrutura atividade da oncoproteína hnRNP K e ligantes." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/60/60136/tde-02102008-164529/.
Повний текст джерелаThe Brazilian Project Genoma Câncer (PGHC) supported by FAPESP and the Ludwig Institute for Cancer Research, intended to identify the genes involved in the most common cases of cancer in Brazil. In this project about a million of gene sequences were identified. The major contribution was made in breast, colorectal and head and neck cancers. The results obtained stimulated the creation of another project, called Genoma Clínico, which intend to develop new trends in treatments and diagnosis of cancer based on the study of expressed genes. Analyzing healthy and neoplasic tissues in different stages, it is possible to identify molecular markers related to the prognosis of cancer, allowing the use of more efficient therapies. The hnRNP K protein was identified as a molecular marker in head and neck cancer, where the objective of this work lies in the application of bioinformatics and molecular modeling strategies by structure-based drug design to identify potential antineoplasic drug candicates that could act against hnRNP K protein. The hnRNP K protein is encountered in all cellular compartments and act, basically, in the gene expression pathways. Its structure is composed by three KH domains that mediate interactions with DNA and RNA molecules. High quality models of KH domains were built by homology modeling. After the virtual screening simulations performed with drug-like compound databases, containing approximately 330.000 compounds, 15 were selected as potential ligands of KH3 domain of hnRNP K. The binding modes suggested for these compounds, by docking simulations, presented a good spatial fit when compared with the virtual receptor sites calculated by molecular interaction fields. Molecular dynamics simulations were performed in order to evaluate de stability of the binding modes suggested. The potential ligands were also evaluated to identify toxicophoric features in its chemical structures.
Veyrier-Cammas, Anne. "Rôle et mode d'action du régulateur traductionnel hnRNP A1 dans les cellules tumorales mammaires." Toulouse 3, 2008. http://thesesups.ups-tlse.fr/335/.
Повний текст джерелаMRNA binding proteins or mRBPs are involved in the regulation, the coordination and the coupling of post-transcriptional gene expression. Modifications in the regulation of their expression and/or activity in cancer contribute to the tumoral development. Our work focused on the study of the translational regulator, hnRNP A1,. We have shown that the translational activity of hnRNP A1 is regulated by its cytoplasmic relocalization upon different stress conditions. We have also observed that a cytoplasmic localization of hnRNP A1 is associated with metastatic relapse and bad prognosis in breast tumors, and we have initiated a study of the effects of this cytoplasmic relocalization on tumorigenesis. This work suggests that regulation of translation by subcellular relocalization of an mRBP may be determinant in cancer
Thomas, Anoushka. "The regulation of p53 transcriptional activity by hnRNPUL-1 and the DNA damage response induced by a novel chemotherapeutic agent, ALX." Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/3945/.
Повний текст джерелаFiset, Stéphan. "Interaction de hnRNP A1/UP1 avec les séquences télomériques humaines et l'ARN de la télomérase." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0017/MQ56900.pdf.
Повний текст джерелаLévesque, Kathy. "hnRNP A2 is a protein involved in the trafficking pathway of HIV-1 genomic RNA." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98748.
Повний текст джерелаBerglund, Frederick M. "Identification of hnRNP-U as a DNA-PK substrate phosphorylated in response to DNA damage." Thesis, University of Dundee, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.505651.
Повний текст джерелаFiset, Stephan. "Interaction de hnRNP A1/UP1 avec les séquences télomériques humaines et l'ARN de la télomérase." Mémoire, Université de Sherbrooke, 2000. http://savoirs.usherbrooke.ca/handle/11143/3182.
Повний текст джерелаBrown, Andrew S. "Identification of a phospho-hnRNP E1 Nucleic Acid Consensus Sequence Mediating Epithelial to Mesenchymal Transition." Kent State University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=kent1437943957.
Повний текст джерелаHu, Wenjun. "Identification of DNA cleavage- and recombination-specific hnRNP co-factors for activation-induced cytidine deaminase." Kyoto University, 2015. http://hdl.handle.net/2433/200494.
Повний текст джерелаCendron, F. "Are the heterogeneous nuclear ribonucleoproteins SQUID and Hrb87F involved in the regulation of circadian rhythmicity in Drosophila melanogaster?" Doctoral thesis, Università degli studi di Padova, 2020. http://hdl.handle.net/11577/3423282.
Повний текст джерелаLa ricerca di nuovi geni coinvolti nel controllo della ritmicità circadiana in Drosophila melanogaster ha permesso di identificare una possibile interazione delle due ribonucleoproteine SQUID e HRB87F con CRYPTOCROME. Nella regolazione molecolare dell’orologio circadiano, si sono evoluti diversi eventi di regolazione post trascrizionale che aggiustano e consolidano l’espressione ritmica dei geni orologio e delle corrispettive proteine, secondo un meccanismo a feedback negativo. Per tale motivo lo scopo di questo lavoro è stato studiare e analizzare il possibile coinvolgimento delle hnRNPs nel controllo post-trascrizionale dell’orologio circadiano in Drosophila. In una fase iniziale, per confermare i risultati ottenuti in precedenza, sono stati condotti esperimenti di Co-Immunoprecipitazione e western-blot in mosche transgeniche in grado di esprimere una versione di CRY associata all’epitopo HA (HACRY) sotto il controllo del driver timGal4. L’anticorpo anti-SQUID ha identificato una proteina nel campione co-immunoprecipitato, confermando l’interazione, mentre il legame con HRB87F è stato osservato mediante l’utilizzo del sistema del doppio ibrido di lievito. In seguito è stato valutato il possibile coinvolgimento dell’orologio circadiano nell’espressione delle hnRNPs nell’intera testa del moscerino. I livelli di espressione del mRNA di Hrb87F mostrano un trend oscillatorio in LD (luce-buio) e DD (buio costante), sia nel wt che nel mutante per0, mentre la proteina oscilla in LD e DD nelle mosche wt, ma non nelle per0, suggerendo un possibile ruolo dell’orologio circadiano nel controllo traduzionale o post-traduzionale della proteina. L’analisi dell’espressione del gene Squid ha dimostrato, invece, che né mRNA né proteina vengono espressi in maniera ritmica, né in LD né DD. Successivamente, è stato studiato l’intervento delle due ribonucleoproteine nella generazione della ritmicità circadiana, analizzando l’attività locomotoria di mosche mutanti per entrambi i geni. Tutti i mutanti hanno riportato un’alterazione della ritmicità circadiana, con una perdita dell’anticipazione dell’attività mattutina in LD e bassi livelli di ritmicità in DD a 29°C, 23°C, 18°C e 15°C. I risultati ottenuti suggeriscono che Squid e Hrb87F possano partecipare alla generazione di un fenotipo ritmico nell’attività locomotoria. Questa analisi è stata completata studiando, inoltre, l’attività locomotoria del mutante squid in condizione di luce costante (LL), poiché esibiva un fenotipo associabile a quello in cui è presente un’alterazione del meccanismo di sincronizzazione della luce; si è visto che, le mosche mutanti presentano un risposta in LL paragonabile al wt, sottolineando un corretto funzionamento del meccanismo di sincronizzazione della luce. Abbiamo analizzato i profili di espressione dei geni period e timeless e delle rispettive varianti dovute a splicing alternativo legato alla temperatura. I risultati ottenuti mostrano che l’espressione è alterata nel mutante Squid, rispetto al controllo wt, sia in LD sia in DD ad ogni temperatura considerata, evidenziando che è presente un elevata attività di splicing. In fine, in collaborazione con la Dott. Milena Damulewicz (Università di Jagiellonian di Kracovia - Polonia), è stata condotta un’analisi dell’espressione di PERIOD nei neuroni orologio in mosche mutanti Squid e wt, mediante immunocitochimica a 18°C e 23°C in LD e DD. Si è visto che sia a 23°C sia a 18°C, l’oscillazione di PER nei neuroni orologio l-LNv, viene persa sia in LD sia in DD, mentre nei neuroni s-LNv sia a 23°C sia a 18°C si assiste a un ritardo nell’accumulo della proteina seguito da una cinetica di degradazione più lenta rispetto ai controlli. L’analisi delle proiezioni del neuropeptide PDF ha evidenziato una profonda disorganizzate nel mutante squid. Nel complesso, tutti questi risultati suggeriscono un coinvolgimento di HRB87F e SQUID nella generazione e nel mantenimento della ritmicità circadiana in Drosophila melanogaster.
Okamoto, Yusuke. "FANCD2 protects genome stability by recruiting RNA processing enzymes to resolve R‐loops during mild replication stress." Kyoto University, 2019. http://hdl.handle.net/2433/242379.
Повний текст джерелаGarneau, Daniel. "Modulation de l'épissage alternatif de Bcl-x par les protéines hnRNP F et H in vitro." Mémoire, Université de Sherbrooke, 2004. http://savoirs.usherbrooke.ca/handle/11143/3390.
Повний текст джерела