Dissertations / Theses on the topic 'Translationally controlled tumour protein'
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Thaw, Paul. "Structural studies of p23'f'y'p : a translationally controlled tumour protein." Thesis, University of Sheffield, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341815.
Full textFoster, William Swinburne. "Translationally Controlled Tumour Protein as a Novel Therapeutic Target in Pulmonary Arterial Hypertension." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/35006.
Full textHayward, K. L. "Lipotoxicity and the role of translationally controlled tumour protein (TCTP) in pancreatic β-cell survival." Thesis, University of the West of England, Bristol, 2014. http://eprints.uwe.ac.uk/22538/.
Full textBruckner, Fernanda Prieto. "The translationally controlled tumor protein is necessary for potyvirus replication." Universidade Federal de Viçosa, 2016. http://www.locus.ufv.br/handle/123456789/11715.
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Conselho Nacional de Desenvolvimento Científico e Tecnológico
Translationally controlled tumor protein (TCTP) é uma proteína amplamente distribuída em eucariotos. Ela está envolvida na regulação de processos básicos como progressão do ciclo celular, crescimento celular, proteção contra estresses e apoptose. Durante a infecção de tomateiro (Solanum lycopersicum) e Nicotiana benthamiana pelo potyvírus Pepper yellow mosaic virus ocorre aumento dos níveis de seu mRNA. Plantas silenciadas para TCTP acumulam menos vírus do que plantas selvagens, mostrando que esta proteína é importante para a infecção por potyvírus. Neste trabalho, o envolvimento da TCTP na infecção por potyvírus foi analisado detalhadamente utilizando-se o potyvírus Turnip mosaic virus (TuMV). Em plantas de N. benthamiana silenciadas para TCTP também ocorre uma diminuição no acúmulo do TuMV quando comparado com plantas não silenciadas. Além disso, plantas superexpressando TCTP de maneira transiente acumularam mais vírus do que plantas controle, confirmando o efeito positivo desta proteína na infecção por diferentes espécies de potyvírus. Para analisar a localização subcelular de TCTP no contexto da infecção, TCTP fusionada a GFP foi co-expressa com TuMV/6K2:mCherry. TCTP co-localiza-se com as vesículas replicativas e com estrutura a globular perinuclear tipicamente observada em células infectadas. O fracionamento de proteínas celulares demonstrou que TCTP está predominantemente na fração solúvel e uma pequena porção se associa com membranas, tanto em plantas sadias quanto em plantas infectadas. A co- localização com vesículas marcadas por 6K2 e a presença de TCTP em frações membranosas da célula sugerem um possível envolvimento desta proteína na replicação viral. Para verificar esta hipótese, protoplastos obtidos a partir de plantas silenciadas para TCTP foram infectados com TuMV e com o mutante TuMV VNN , o qual não é capaz de replicar-se. Os resultados demonstraram que o acúmulo de TuMV é reduzido em protoplastos silenciados, indicando que TCTP é necessária para a replicação. O acúmulo da proteína TCTP durante a infecção também foi avaliado. A infecção viral induz o aumento dos níveis de mRNA mas não de proteína, sugerindo que o mRNA que codifica TCTP atue na replicação. Desta forma, foi analisado se expressão de um RNA não traduzível de TCTP possui efeito sobre a infecção viral. Os resultados mostraram que apenas a expressão de um RNA traduzível é capaz de aumentar a infecção viral, indicando que a proteína TCTP, ou que a tradução se seu mRNA, é importante para a replicação viral.
The translationally controlled tumor protein (TCTP) is widely distributed among eukaryotes. It is involved in the regulation of basic processes such as cell cycle progression, cell growth, stress protection and apoptosis. During tomato (Solanum lycopersicum) and Nicotiana benthamiana infection by the potyvirus Pepper yellow mosaic virus, an increase of TCTP mRNA levels was observed. Plants silenced for TCTP accumulate fewer viruses than control plants, showing the importance of that gene for potyvirus infection. In this work, TCTP involvement in potyvirus infection was analyzed in details using the potyvirus Turnip mosaic virus (TuMV). N. benthamiana plants silenced for TCTP accumulated fewer viruses than non-silenced plants. In addition, plants overexpressing TCTP transiently accumulated more viruses than control plants, confirming that TCTP has a positive effect on infection by different potyviruses. To study TCTP subcellular localization in potyvirus infected plants, TCTP fused to GFP was co- expressed with TuMV/6K2:mCherry. Confocal analysis has shown that TCTP co- localizes with 6K2-tagged structures such as replicative vesicles and the perinuclear globular structure that is typically observed in potyvirus-infected cells. Cellular fractioning demonstrated that TCTP is mainly present in the soluble fraction but is also associated with membranes. The co-localization of TCTP with 6K2-tagged vesicles and its presence in cellular membranous fractions suggests a possible involvement of TCTP in virus replication. To test this hypothesis, protoplasts obtained from TCTP silenced plants were infected with TuMV and its mutant TuMV VNN , which is defective for replication. The results showed that TuMV accumulation is reduced in silenced protoplasts, indicating that TCTP is necessary for replication. TCTP accumulation during infection was also analyzed. Viral infection induces TCTP mRNA expression, but not protein accumulation, suggesting that the TCTP mRNA and not the protein has a role in viral infection. To check this, we expressed a non-translatable form of TCTP RNA in plants and analyzed its effect in virus accumulation. The results showed that only the expression of a translatable RNA resulting in protein production is able to increase virus infection, indicating that the protein and/or the translation of TCTP is important for potyvirus replication.
陳漢文 and Hon-man Chan. "Overexpression of translationally controlled tumor protein (TCTP) predisposes to hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hdl.handle.net/10722/193056.
Full textpublished_or_final_version
Clinical Oncology
Doctoral
Doctor of Philosophy
Karafin, Teele. "Etude de la fonction de Translationally Controlled Tumor Protein (TCTP) dans différents modèles génétiques dans la souris." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS211.
Full textTCTP is a 20 kDa protein frequently encountered as a dimer. It is highly conserved through phylogeny and is present inn yeast, plants, invertebrates and mammals. It is localized in all compartments of the cell: nucleus, cytoplasm, membranes. This protein is highly abundant in stem cells and during the exponential growth, including in cancer cells. It mainly functions as a survivor factor. TCTP has been described as interacting with multiple proteins, including p53, MDM2, Bcl-xL and TSAP6. The purpose of my work is to better characterize these functions of TCTP; we therefore studied its interactions in vitro, but mostly in vivo, using different murine genetic models
Thébault, Stéphanie. "Etude des complexes entre TCTP (Translationally Controlled Tumor Protein) et ses partenaires." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T024.
Full textAdam Telerman’s team research focuses on tumor reversion, a rare process in which cancer cells lose their malignant phenotype, and therefore become revertant. Many key proteins were showed to be involved in this transformation, including TCTP (translationally Controlled Tumor Protein). TCTP protein is also involved in apoptosis regulation by interacting and strengthening the anti-apoptotic activity of Mcl-1 and Bcl-xl, two proteins from Bcl-2 family
Andrade, Patrícia Oliveira. "Involvement of Translationally controlled tumor protein in Tomato yellow spot virus infection." Universidade Federal de Viçosa, 2017. http://www.locus.ufv.br/handle/123456789/21427.
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Fundação de Amparo à Pesquisa do Estado de Minas Gerais
Os vírus são as formas de vida mais abundantes e geneticamente diversas conhecidas em nossa biosfera. Para infectar hospedeiros com sucesso, os vírus manipulam componentes celulares do hospedeiro, recrutando fatores do hospedeiro necessários para replicação, infeção e transmissão. Além disso, os vírus precisam suplantar diversas estratégias de defesa do hospedeiro levando a um complexo mecanismo de coevolução que envolve diversas interações. Diferentes vírus podem interagir com componentes celulares do hospedeiro de forma semelhante. Foi demonstrado que a presença da proteína translationally controlled tumor protein (TCTP) é necessária para o estabelecimento de uma infecção eficiente por potyvírus. TCTP é uma proteína multifuncional encontrada em quase todos os eucariotos envolvida no crescimento celular, homeostase de íons, reparo de danos no DNA e possuí atividade anti-apoptótica. Apesar de inúmeros estudos com TCTP, o envolvimento desta proteína na infecção viral ainda não é totalmente compreendido. Devido a sua diversidade funcional, é possível imaginar que TCTP possa ser um fator do hospedeiro envolvido em infeções causadas por vírus de diferentes grupos. Desta forma, neste trabalho, foi avaliado o efeito de TCTP na infecção por begomovírus. Para isso, plantas de Nicotiana benthamiana com TCTP silenciada por VIGS foram utilizados para estudar o efeito da TCTP na infecção pelo begomovírus Tomato yellow spot virus (ToYSV). O silenciamento de TCTP levou a um maior acúmulo de vírus, sugerindo que TCTP é um fator do hospedeiro envolvido no processo de defesa á infecção viral. Além disso, o mRNA de TCTP é altamente estruturado em mamíferos e está relacionado com a indução de resposta a infecções por diferentes vírus. Por ser um mRNA altamente estruturado é razoável supor que o mRNA de TCTP pode ser alvo do processo de silenciamento pós transcrisional da planta levando à produção de pequenos RNAs de interferência (siRNAs) através da clivagem por proteínas Dicer e os siRNAs gerados podem regular a expressão de genes endógenos do hospedeiro. Desta forma, foi realizada uma análise in silico para avaliar os possíveis siRNAs gerados a partir do silenciamento do mRNA de TCTP e os possíveis alvos desses siRNAs. Genes que podem estar envolvidos em infecção viral, como aqueles que codificam proteína kinases, proteínas envolvidas na via de ubiquitinação, fatores de transcrição e tradução e proteínas de ligação ao cálcio foram alguns dos genes identificados como possíveis alvos destes siRNAs.
Viruses are the most abundant and genetically diverse life forms known in our biosphere. To successfully infect hosts, viruses manipulate host cellular components, recruiting host factors necessary for replication, infection, and transmission. In addition, viruses need to supplant various host defense strategies, leading to a complex coevolution mechanism involving virus-host interactions. Different viruses can interact with host cell components similarly or even antagonistic. The presence of the protein translationally controlled tumor protein (TCTP) has been shown to be necessary for the establishment of an efficient potyvirus infection. TCTP is a multifunctional protein found in almost all eukaryotes and is involved in cell growth; ions homeostasis; DNA damage repair and anti-apoptotic activity. Despite numerous studies with TCTP, the involvement of this protein in viral infection is not yet fully understood. Due to its functional diversity, it is possible to imagine that TCTP may be a host factor involved in infections caused by viruses of different groups. Thus, in this work, the effect of TCTP on begomovirus infection was evaluated. Nicotiana benthamiana plants silenced for TCTP by VIGS experiments were used to study the effect of TCTP expression on infection by the begomovirus Tomato yellow spot virus (ToYSV). TCTP silencing led to higher accumulation of the virus, suggesting that TCTP is a host factor involved in viral infection defense process. Furthermore, TCTP mRNA is highly structured in mammals and is related to the induction of defense response to different viruses. Because it is a highly structured mRNA, it is reasonable to assume that TCTP mRNA may be the target of the plant post transcription gene silencing mechanism, leading to the production of small interfering RNAs (siRNAs) by the cleavage of Dicer proteins and the siRNAs generated might regulate the expression of host endogenous genes involves in virus infection. In silico analysis was performed to evaluate the possible siRNAs generated from the silencing of TCTP mRNA, and the respective targets of this siRNAs. Genes involved in viral infection, such as those encoding protein kinases, proteins involved in the ubiquitination pathway, transcription and translation factors, and calcium binding proteins were some of the genes identified as possible targets of these predicted siRNAs.
Carvalho, Márcio de [UNESP]. "Estudo do papel da TCTP (Translationally Controlled Tumour Protein) na resposta ao estresses bióticos e abióticos em plantas." Universidade Estadual Paulista (UNESP), 2010. http://hdl.handle.net/11449/92453.
Full textConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
O gene que codifica a TCTP (Translationally Controlled Tumour Protein) está presente em todos os eucariontes e o seu produto está envolvido em diferentes processos celulares. Embora bem caracterizada em mamíferos, poucos são os trabalhos disponíveis na literatura relacionados à análise da TCTP em plantas. No presente trabalho, a expressão do gene que codifica a TCTP em tomateiros foi analisada em situações de estresse biótico e abiótico. No estresse abiótico, as plantas de tomate foram submetidas a dano mecânico nas folhas, e essas coletadas após 4, 8 e 12 horas. No estresse biótico, duas espécies virais foram inoculadas mecanicamente nas plantas de tomate, o Cucumber mosaic virus (CMV) e o Pepper Yellow Mosaic Virus (PepYMV), respectivamente, e as folhas sistemicamente inoculadas foram coletadas após 25 dias. Um aumento na expressão da TCTP foi constatado em resposta ao estresse biótico, sendo de 1,3x em relação ao controle não inoculado na infecção pelo CMV, e de 1,4x na infecção pelo PepYMV. No estresse mecânico, o pico de expressão ocorreu após 4 horas com um aumento de 3,4x em relação ao controle não tratado, com posterior redução nos demais tempos. Adicionalmente, plantas transgênicas de tabaco capazes de superexpressar a TCTP de tomate foram geradas a fim de determinar o papel dessa proteína na infecção pelo PepYMV. Quando as linhagens transgênicas geradas foram inoculadas com o PepYMV observou-se, aos 14 dias após a inoculação (DAI), um aumento na concentração viral (1,8x) em relação às plantas de tabaco não transformadas, sendo o mesmo verificado aos 21 DAI (1,6x). Essa diferença, entretanto, não foi mais observada aos 28 DAI. Esses dados confirmam a relação funcional da TCTP com a resposta de defesa das plantas aos estresses bióticos e abióticos
Not available
Carvalho, Márcio de. "Estudo do papel da TCTP (Translationally Controlled Tumour Protein) na resposta ao estresses bióticos e abióticos em plantas /." Botucatu, 2010. http://hdl.handle.net/11449/92453.
Full textBanca: Fábio Tebaldi Silveira Nogueira
Banca: Jomar Patricío Monteiro
Resumo: O gene que codifica a TCTP (Translationally Controlled Tumour Protein) está presente em todos os eucariontes e o seu produto está envolvido em diferentes processos celulares. Embora bem caracterizada em mamíferos, poucos são os trabalhos disponíveis na literatura relacionados à análise da TCTP em plantas. No presente trabalho, a expressão do gene que codifica a TCTP em tomateiros foi analisada em situações de estresse biótico e abiótico. No estresse abiótico, as plantas de tomate foram submetidas a dano mecânico nas folhas, e essas coletadas após 4, 8 e 12 horas. No estresse biótico, duas espécies virais foram inoculadas mecanicamente nas plantas de tomate, o Cucumber mosaic virus (CMV) e o Pepper Yellow Mosaic Virus (PepYMV), respectivamente, e as folhas sistemicamente inoculadas foram coletadas após 25 dias. Um aumento na expressão da TCTP foi constatado em resposta ao estresse biótico, sendo de 1,3x em relação ao controle não inoculado na infecção pelo CMV, e de 1,4x na infecção pelo PepYMV. No estresse mecânico, o pico de expressão ocorreu após 4 horas com um aumento de 3,4x em relação ao controle não tratado, com posterior redução nos demais tempos. Adicionalmente, plantas transgênicas de tabaco capazes de superexpressar a TCTP de tomate foram geradas a fim de determinar o papel dessa proteína na infecção pelo PepYMV. Quando as linhagens transgênicas geradas foram inoculadas com o PepYMV observou-se, aos 14 dias após a inoculação (DAI), um aumento na concentração viral (1,8x) em relação às plantas de tabaco não transformadas, sendo o mesmo verificado aos 21 DAI (1,6x). Essa diferença, entretanto, não foi mais observada aos 28 DAI. Esses dados confirmam a relação funcional da TCTP com a resposta de defesa das plantas aos estresses bióticos e abióticos
Abstract: Not available
Mestre
Kim, Kevin Dae Keon. "The Translationally Controlled Tumor Protein (TCTP) associates to and destabilizes the Circadian Factor Period 2 (Per2)." Thesis, Virginia Tech, 2010. http://hdl.handle.net/10919/76848.
Full textMaster of Science
Tuijnder, Marcel. "Biological models of tumor reversion." Paris 7, 2005. http://www.theses.fr/2005PA077085.
Full textBaylot, Virginie. "L'analyse des mécanismes d'action d'Hsp27 a mis en évidence TCTP comme nouvelle cible thérapeutique des cancers de la prostate résistants à la castration." Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM4021.
Full textProstate cancer (PC) is the second most common cause of cancer-related mortality in men in the Western world. Androgen ablation (castration-therapy) is usually the initial therapy in patients with advanced or metastatic disease. Unfortunately, the disease gradually progresses to a metastatic castration-resistant (CR) state, which remains incurable. Recently, the involvement of Hsp27 (Heat Shock Protein 27) in CR progression has been identified and an oligonucleotide antisense (OGX-427), inhibitor of Hsp27 is currently in phase II/III clinical trials to treat CRPC. In order to understand Hsp27 mechanisms of action in CR progression, we started to screen for Hsp27 partner proteins by using two-hybrid system. My PhD work has reported that Translationally Controlled Tumor Protein (TCTP) was a new Hsp27 protein partner that mediated Hsp27 cytoprotection in CRPC and that TCTP expression was absent in normal prostate tissues. We have further found that CR progression correlated with TCTP overexpression, the loss of P53 and that TCTP silencing using an antisense was able to restore P53 expression and function. This study suggests for the first time that castration-sensitivity is directly linked to P53 expression. In addition, we revealed exciting new aspects of the Hsp27 involvement in essential metabolic and cellular processes such as DNA repair and mRNA splicing. In summary, my PhD results have provided an enriched understanding of Hsp27 mechanisms of cytoprotection contributing to CRPC progression and opened a new promising field of research for multi-target therapeutic approaches
Duflaut, Dominique. "Etudes moléculaires et fonctionnelles des gènes TSAP6 (Tumor Suppressor Activated Pathway 6) et TCTP (Translationally Controlled Tumor Protein) : cibles pharmacologiques anti-tumorales." Phd thesis, Université Paris Sud - Paris XI, 2008. http://tel.archives-ouvertes.fr/tel-00293914.
Full textTpt1, codant pour la protéine TCTP, est le gène le plus sous-exprimé lors de la réversion tumorale. L'analyse du cristal de TCTP humain montre une forte homologie entre ses hélices H2-H3 et les hélices H5-H6 de Bax. Grâce à ses hélices, TCTP inhibe l'apoptose induite par Bax au niveau des mitochondries. En effet, nous démontrons que TCTP, entre autres par le biais de ces hélices, empêche la dimérisation de Bax.
Nous avons aussi développé une lignée de souris TCTP knockout qui présentent une létalité embryonnaire précoce.
En parallèle, nous avons étudié TSAP6, qui encode pour une protéine à 6 domaines transmembranaires et qui est une cible transcriptionnelle directe de la p53. Nous avons établi une lignée murine TSAP6 knockout présentant une anémie microcytaire avec une splénomégalie. Les réticulocytes issus des souris knockout présentent un retard de maturation et une anomalie de sécrétion du Récepteur à la Transferrine par les exosomes. De manière plus générale, les résultats obtenus montrent, in vivo, que TSAP6 contrôle la sécrétion des exosomes induite par activation de la P53. Nous montrons aussi que la Sertraline et la Thioridazine empêchent la formation du complexe TSAP6-TCTP.
Chabrier, Amélie. "Réversion tumorale pour le traitement du cancer : conception et synthèse de nouveaux inhibiteurs de la TCTP (« Translationally Controlled Tumor Protein »)." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS437.
Full textTumor reversion is a natural process that was discovered for the first time in the early 1960s. It is a biological phenomenon by which highly tumorigenic cells lose at great extent or entirely their malignant phenotype. This is a rare molecular program (one cell for a million cancer cells) which suggests that organic compounds could stimulate this process and form a new class of medicinal products susceptible to treat cancer patients. For those purposes, the translationally controlled tumor protein (TCTP) has been identified as a major therapeutic target of tumor reversion. Consequently, identification of products that are capable of stimulating this phenomenon, by TCTP inhibition, will constitute a promising new strategy for the treatment of the disease.In this context, the goal of this thesis is to design and synthesis new TCTP inhibitors, analogues of sertraline. This latter is a widely used antidepressive drug but it also shows significant efficacy throughout the tumor reversion program. In the second part, those analogues will undergo diverse biological essays (affinity, cytotoxicity, ADMET process…) in the aim of identifying a potential lead compound which will be evaluate under in vivo conditions. Moreover, this research is also focus on the optimizations of the first synthetic route and the development of innovative methods to access to those new TCTP inhibitors
Lavoie, Jessie. "Proteomic Analysis Identifies Translationally Controlled Tumor Protein as a Potential Novel Mediator of Occlusive Vascular Remodeling in Pulmonary Arterial Hypertension." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/24243.
Full textBrioudes, Florian. "Regulation of organ morphogenesis : Functional analysis of the TRANSLATIONALLY CONTROLLED TUMOR PROTEIN and of the transcription factor BIGPETALp in Arabidopsis thaliana." Lyon, Ecole normale supérieure, 2010. http://www.theses.fr/2010ENSL0602.
Full textIn multicellular organisms, morphogenesis requires the tight regulation of cell proliferation, growth and death, in order to form organs with specific shapes and sizes. During my Ph. D. Thesis work, I addressed the biological roles of two genes involved in organ morphogenesis in the plant model species Arabidopsis thaliana, namely TRANSLATIONALLY CONTROLLED TUMOR PROTEIN (AtTCTP) and BIGPETALp (BPEp). I showed that AtTCTP is essential for plant development and that AtTCTP controls the cell cycle progression, particularly at the G1/S transition. Furthermore I showed that this function of AtTCTP in regulating cell proliferation is evolutionarily conserved between plants and animals. BPEp encodes a bHLH transcription factor that regulates cell elongation in developing petals. I showed that the accumulation of BPEp transcript is positively controlled by a signal initiated by the phytohormone jasmonate and that this regulation occurs at the post-transcriptional level. I also demonstrated a role of jasmonate in the control of cell expansion during petal growth. Search for BPEp putative binding proteins identified an AUXIN RESPONSE FACTOR (ARF8) as putative interactor of BPEp. Studies of molecular and genetic interaction with ARF8 demonstrated that BPEp is inscribed in a network regulated by auxin, a second phytohormone. In summary my results together help to better understand how plants regulate organogenesis, thanks to the functional characterization of the conserved key player TCTP, which is involved in the control of mitotic growth, and of the phytohormone-dependent transcription factor BPEp, which regulates post-mitotic growth
Susini, Laurent. "Implication de Siah-1 dans la dégradation des protéines et dans l' expression des gènes durant la réversion tumorale." Paris 7, 2003. http://www.theses.fr/2003PA077115.
Full textBruckner, Fernanda Prieto. "Aspectos da interação entre a proteína TCTP e o potyvírus PepYMV na infecção de tomateiro e Nicotiana benthamiana." Universidade Federal de Viçosa, 2012. http://locus.ufv.br/handle/123456789/5355.
Full textCoordenação de Aperfeiçoamento de Pessoal de Nível Superior
Viruses are organisms with small genomes of simple organization, which coding about 3 to encode 10 viral proteins. The success of the infection depends on the manipulation of the cell by the virus, by means of complex interactions occurring between viral factors and host factors. The induced changes by virus infection include cell morphology changes, cell cycle changes and alterations in gene expression, among others. Understanding the processes that favor viral infection necessarily involves the study of virus-host interactions. In order to better understand the processes related to infection by tomato potyvirus Pepper yellow mosaic virus (PepYMV) a subtractive library was built 72 hours after infection. Several genes were identified as induced or repressed by viral infection. Among the induced genes, is the gene encoding the Translationally controlled tumor protein (TCTP). TCTP protein is highly conserved in all eukaryotes. Its functions are related to growth control and cell cycle, anti-apoptotic activity, and response to different biotic and abiotic stresses. The involvement of this protein in infection PepYMV has not been established, but studies in a strain of transgenic tomato plants silenced for TCTP showed that the silenced plants have a lower accumulation of PepYMV, indicating that TCTP promotes viral infection. In this study, we sought to advance the understanding of mechanisms involving TCTP in the process of infection by PepYMV. N. benthamiana plants silenced by VIGS TCTP were used to study the effect of silencing in viral infection, and the silenced plants accumulate fewer viruses in early stages of virus infection. Individual expression of viral proteins in N. benthamiana identified P3 and CP as capable of inducing TCTP expression at similar levels to those induced during PepYMV infection, and expression of NIb reduced expression of TCTP. The verification of direct interactions occurrence between viral proteins and TCTP by double-hybrid assay showed that TCTP not interact separately with any of the proteins of viral origin. Purification of proteins of health and infected N. benthamiana plants by affinity with TCTP identified several proteins that putativaly interacts with TCTP. As in two hybrid assay, interactions involving PepYMV proteins were not detected. These results sugests that TCTP actuation must involve the formation of protein complexes involving viral and plant proteins or contribute indirectly to PepYMV infection, without involving direct interactions between TCTP and viral proteins.
Os vírus são organismos com genomas pequenos, de organização simples, que codificam em média 3 a 10 proteínas. O sucesso da infecção depende da manipulação da célula pelo vírus, por meio de interações complexas que ocorrem entre fatores virais e fatores do hospedeiro. As modificações induzidas na célula incluem alterações morfológicas, alteração do ciclo celular e na expressão gênica, entre outras. A compreensão dos processos que favorecem a infecção viral passa necessariamente pelo estudo de interações vírus-hospedeiro. No intuito de compreender melhor os processos relacionados à infecção de tomateiros pelo potyvírus Pepper yellow mosaic virus (PepYMV) uma biblioteca subtrativa foi construída 72 horas após a infecção. Diversos genes cuja expressão foi alterada pela infecção foram identificados. Dentre os genes induzidos, se encontra o gene que codifica a Translationally controlled tumor protein (TCTP). A proteína TCTP é altamente conservada em todos os eucariotos. Suas funções estão relacionadas a controle do crescimento e ciclo celular, atividade anti-apoptótica, e resposta a diferentes tipos de estresses abióticos e bióticos. O envolvimento desta proteína na infecção pelo PepYMV ainda não foi estabelecido, porém estudos em uma linhagem de tomateiro transgênica silenciadas para a TCTP, mostraram que as plantas silenciadas apresentam um menor acúmulo de PepYMV, indicando que a TCTP favorece a infecção por este vírus. Neste trabalho, buscou-se avançar na compreensão dos mecanismos que envolvem a TCTP no processo de infecção pelo PepYMV. Plantas de Nicotiana benthamiana silenciadas para TCTP por VIGS (Virus Induced Gene Silence) foram utilizadas para estudar o efeito do silenciamento na infecção viral, sendo que as plantas silenciadas acumularam menos vírus no início da infecção. A expressão individual das proteínas de origem viral em N. benthamiana identificou a P3 e a CP como capazes de induzir a expressão de TCTP em níveis semelhantes aos observados durante a infecção pelo PepYMV, sendo que a expressão da proteína NIb reduziu a expressão de TCTP. A verificação da ocorrência de interações diretas entre a TCTP e as proteínas virais, por ensaio de duplo híbrido, mostrou que a TCTP não interage separadamente com as proteínas de origem viral. A purificação de proteínas de plantas de N. benthamiana, sadias e infectadas, por afinidade com a TCTP identificou diversas proteínas que possivelmente 7 interagem com a TCTP. Assim como no ensaio de duplo híbrido, a interação com proteínas virais não foi detectada. Estes resultados sugerem que o papel da TCTP deve envolver a formação de complexos proteicos entre proteínas virais e da planta, ou favorecer a infecção de forma indireta.
Wippermann, Barbara. "Functional characterisation of the TCTP gene : a role in regulation of organ growth." Thesis, Lyon, École normale supérieure, 2013. http://www.theses.fr/2013ENSL0814.
Full textThe growth of a multicellular organism and its size determination require the tight regulation of cell proliferation, cell differentiation, cell growth and apoptosis. These processes are influenced by the nutritional state of the organism, its environmental conditions and hormonal signals. Translationally controlled tumor protein (TCTP) is an essential regulator of growth in plants and animals. In plants it controls mitotic growth, whereas in animals, it controls mitotic and post-mitotic growth. One of the important pathways involved in the control of growth in response to nutrients is the Target of Rapamycin (TOR) pathway. In Drosophila, dTCTP was proposed to act a positive regulator upstream of TOR, although this role remains a matter of debate in the animal field.During the past 3 years of my PhD. thesis, I addressed the question whether plant TCTP acts upstream of TOR to control organ growth. I studied the impact of nutrient availability and hormones on TCTP role to control growth in plants and vice versa. Finally, I examined why plant TCTP does not control post-mitotic cell expansion growth, conversely to animal TCTP using a structure-function approach.In animals, TCTP was proposed to act as a positive activator upstream of the TOR pathway. In plants, my data support a model in which AtTCTP acts independently from the plant TOR pathway, thus in contrast to what has been proposed in animals. TCTP loss of function leads to delay of embryo development and death. Nutrient supplement rescues this embryos lethality. First, I demonstrate that embryos grown on nutrients lacking sucrose or glutamine fail to develop correctly. My data demonstrate that in vitro AtTCTP is not essential to the uptake, the use of and the response to the nutrients glucose, sucrose or glutamine. Taken together, these results reevaluate the role of AtTCTP as a growth regulator controlling mitotic growth independently from the TOR pathway and likely from nutrient related signaling pathways. Interestingly, my data also show that AtTCTP controls growth independently from auxin flux or homeostasis and that auxin-induced growth can occur without TCTP. To address why plant TCTP do not control post-mitotic growth conversely to animal counterpart, I performed protein domain swaps and created chimera proteins between Arabidopsis AtTCTP and Drosophila dTCTP. The rational was to identify protein domains that differentiate plant and animal TCTPs with regard to post-mitotic growth control. Most of chimera proteins were instable and I was unable to complement tctp loss of function in Drosophila. I performed a structure based modeling to understand this phenotype and the outcome is discussed in my PhD thesis.Altogether my results improve the understanding of plant morphogenesis by reevaluating the role of the central growth regulator TCTP
Savarin, Julie. "Caractérisation de la voie TCTP (TRANSLATIONALLY CONTROLLED TUMOR PROTEIN) chez Arabidopsis thaliana : identification des régulateurs de son accumulation et importance de la voie au cours du développement embryonnaire." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSEN001.
Full textTCTP (Translationally Controlled Tumor Protein) is strongly conserved among eukaryotes. It is a vital protein implicated in various major processes, and its absence leads to early embryolethality in many organisms. In plants as in animals, TCTP is a key factor of growth and development. Implicated in apoptosis and DNA repair, TCTP is also an enhancer of cell proliferation, and is a key element of tumorigenesis. Major functions of TCTP are conserved between plants and animals, but upstream factors are not known yet. Using a genetic screen on the model plant Arabidopsis thaliana, the principal goal of this thesis was to discover regulators of TCTP.In parallel, the impact of TCTP knockout on auxin and cytokinin pathways during embryo development was investigated
Hassan, Dhiya. "Forced Overexpression of Translationally Controlled Tumor Protein (TCTP/TPT1) Induces a Growth-Dysregulated Phenotype in Endothelial and Smooth Muscle Cells: Role of TCTP Exosomal Export in Paracrine Cell-Cell Signaling Induced by Endothelial Injury." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/38674.
Full textThiele, Holger. "Struktur und Funktion des Gens für das translationell kontrollierte Tumorprotein (TCTP)." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2000. http://dx.doi.org/10.18452/14496.
Full textThe translationally controlled tumor protein (TCTP) is a conserved eukaryotic protein, which is involved in the pathogenesis of allergic diseases. In atopic children it has been reported to mediate histamine release from basophilic leukocytes in an IgE dependent way. The underlying mechanism, however, is unknown. TCTP is characterized by an efficient binding to tubulin of cytoskeletal structures and by a high calcium affinity. Its synthesis is regulated at the transcriptional and translational level. A specific function in tumor cells, which was assumed initially, could not be confirmed. The gene coding for TCTP is called TPT1. To understand the molecular basis for the control of TCTP expression structure and function of the human and rabbit TPT1 genes were investigated including their promoter regions. The first mammalian TPT1 gene (rabbit) was cloned and sequenced. It consists of 3.8 kb and is interrupted by five introns. Two mRNAs of 843 and 1163 nt length are transcribed differing in their 3'untranslated regions. They are generated by alternative polyadenylation. Furthermore genomic recombinants were isolated containing the human TPT1 gene and a preliminary structure of the gene was established. The human gene has the same intron/exon architecture as the rabbit gene just differing in the length of its introns. Human multi-tissue dotblots revealed an identical transcription pattern for both mRNAs. The concentration of the TCTP mRNAs differed up to the factor 100 between different tissues, indicating distinct tissue specificity in transcriptional control. 1.2 kb 5'flanking promoter structures were analyzed for transcription factor binding sites. For functional studies TPT1 promoter fragments were fused to the chloramphenicol acetyltransferase (CAT) reportergene and assayed by cell transfection and CAT enzyme activity. A basic promoter of 66 bp length containing a TATA box could be defined. Maximal promoter activity of 90% compared to the strong thymidine kinase promoter was associated with a fragment of 290 bp containing a SP-1, two AP-1/CREB and two ETS binding sites. This is a common feature of genes like TPT1, which are inducible by phorbolesters and lipopolysaccharides. Furthermore, numerous processed TPT1 pseudogenes were found spread through the rabbit genome. Six pseudogenes and their flanking genomic integration sites were sequenced. They represented both mRNA types and were at least 99% homologous to the corresponding mRNAs. In all pseudogenes the open reading frames were retained and in two of them the original amino acid sequence was even conserved completely. The 5'flanking region of one pseudogene was tested for transcriptional activity by CAT assays and revealed an activity of about 15% of the authentical TPT1 promoter. This could suggest a possible expression of TPT1 pseudogenes in vivo.
Branco, Remi. "Functional analysis of a putative master regulator of plant development, the Translationally-Controlled Tumour Protein." Phd thesis, 2020. http://hdl.handle.net/1885/209920.
Full textLeclercq, Tamara Marie. "Regulation of sphingosine kinase by interacting proteins." Thesis, 2010. http://hdl.handle.net/2440/64752.
Full textThesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2010
Roque, Cláudio André Gouveia Martins. "A Role for Tctp in Neural Circuitry Formation." Doctoral thesis, 2015. http://hdl.handle.net/10316/28232.
Full textWith 86 billion neurons in the human brain, the ordered array of neuronal pathways is an exceptionally complex web of accurately connected axonal and dendritic processes, ultimately allowing us to perceive the world and respond consciously to it. Precise wiring of the nervous system is therefore the cornerstone of its intricate functions. Neuronal connectivity begins to take shape during embryonic development, when post-migratory newborn neurons send out a single threadlike axon that extends in a highly directed manner to the vicinity of its appropriate target region. Axon pathfinding relies on molecular ‘guideposts’ presented in the embryonic landscape and integrated by the growth cone, an amoeboid, sensory structure at the tip of developing axons first identified by the legendary Ramón y Cajal. Studies in the past three decades have revealed that a certain degree of functional autonomy is endowed upon this cellular outpost, perhaps best exemplified by the demonstration that axons separated from their cell bodies can still navigate correctly in vivo. It is now evident that this flexibility partly arises from the local regulation of the axonal proteome in response to extracellular cues. The local translation of new proteins elicited by these factors allows for rapid alterations in cytoskeleton dynamics, guidance receptor expression, substrate adhesion, as well as promoting axonal and mitochondrial maintenance. The recent appreciation of the complexity of the axonal transcriptome, with thousands of mRNAs identified, clearly illustrates the functional significance of this homeostatic mechanism. Here, I pioneered the study of translationally controlled tumor protein (Tctp) in the context of neural connectivity using the Xenopus laevis (African clawed frog) retinotectal projection as an in vivo model system. Tctp is an evolutionary conserved pro-survival protein implicated in cell growth and particularly well-studied in cancer pathogenesis, where its expression is often found upregulated and correlates with indicative markers of aggressive disease. Significantly, across diverse neuronal populations, including retinal ganglion cells, the tpt1 transcript, which encodes for Tctp, is ranked among the most enriched in the axonal compartment, suggestive of an unexplored relevant role in neurobiology. My most significant original contribution to knowledge is the identification of Tctp as a cell-autonomous checkpoint for axon development through its support of mitochondrial homeostasis. Specifically, Tctp deficiency during embryogenesis results in shorter retinotectal projections that fail to reach their target at the appropriate developmental window. Tctp-depleted axons exhibit mitochondrial dysfunction, decreased mitochondrial density and defects in mitochondrial dynamics, but Tctp knockdown embryos have intact mitochondrial biogenesis and mass, arguing for a phenotype with pre- dominantly axonal repercussions. Furthermore, I document that axonal Tctp interacts with Bcl-2 pro-survival oncoproteins myeloid cell leukemia 1 (Mcl1) and Bcl-2-like protein 1 (Bcl-XL), and that Caspase-3 activation and increased P53 levels are found in growth cones depleted of Tctp. Overall, the data I have collected over the course of my research indicate that Tctp regulates axon development by impacting on the homeostatic mechanisms of the neuron. My findings thus suggest a novel and fundamental role for Tctp in vertebrate neural circuitry formation.
Com os seus cerca de 86 mil milhões de neurónios [1], o cérebro humano é constituído por uma rede intrincada de processos axonais e dendríticos complexamente interligados, e que, como um todo coerente, nos permite reconhecer sinais com origem no meio externo e responder de forma consciente sobre este. A formação de ligações precisas entre as diversas áreas do sistema nervoso assume, portanto, um papel fundamental no garante das suas funções. Numa primeira fase, os programas de conectividade neuronal desenvolvem-se no decurso da embriogénese. Em concreto, após a formação e subsequente migração do neurónio, este estende um axónio que se expande de modo estereotipado até à vizinhança do seu alvo pós-sináptico. Os mecanismos de navegação axonal dependem de uma sequência de marcos moleculares distribuídos pelo sistema nervoso embrionário, os quais são integrados ao nível do cone de crescimento, uma estrutura ameboide com capacidades sensoriais e motoras, existente no extremo distal do axónio. Ao longo das últimas três décadas, um vasto leque de estudos foi permitindo perceber que o cone de crescimento é dotado de um certo grau de autonomia funcional [2], facto claramente ilustrado pela capacidade inalterada revelada por axónios embrionários seccionados – isto é, separados dos seus corpos celulares – para se orientarem corretamente in vivo [3]. Sabe-se hoje que esta flexibilidade de atuação advém, em parte, da regulação local do proteoma axonal promovida pelos sinais moleculares presentes no meio extracelular embrionário. A tradução local de novas proteínas despoletada por estes factores permite, por exemplo, alterações rápidas ao nível do citoesqueleto [4-6] e da expressão de receptores na membrana celular do cone de crescimento [7], assim como potenciar mecanismos de manutenção axonal e mitocondrial [8-10]. É, no entanto, o carácter transversal do transcriptoma axonal – o número de espécies de ARNm localizados no compartimento axonal situa-se na ordem dos milhares [11-15] – que porventura nos dá verdadeiramente conta da importância funcional deste processo celular. Nos estudos laboratoriais conducentes a esta tese, foi estudada a participação da Tctp (do acrónimo inglês, translationally controlled tumor protein) nos processos de conectividade neuronal, usando como modelo a projeção retinotectal da rã-de-unhas -africana (Xenopus laevis). A Tctp é uma proteína conservada filogeneticamente [16], relevante ao nível de processos de sobrevivência [17] e de crescimento celular [18, 19], e bem caracterizada em particular no âmbito da oncogénese [20]. A motivação inicial para estudar a Tctp neste contexto surgiu da identificação do ARNm que codifica a Tctp entre os mais abundantemente expressos no compartimento axonal de diversas populações neuronais [11-14], incluindo em células ganglionares da retina, indicando que esta proteína detém um papel local relevante, mas por explorar, no campo da neurobiologia. A minha contribuição original mais significativa para o conhecimento prende-se com a identificação do envolvimento da Tctp na regulação do desenvolvimento axonal através da sua função de suporte à homeostasia mitocondrial. Especificamente, a depleção da Tctp durante a embriogénese resulta em projeções retinotectais que não granjeiam alcançar a zona-alvo no mesencéfalo aquando do estádio de desenvolvimento normal. Os axónios deficitários em Tctp apresentam uma disfunção e menor densidade mitocondrial, bem como dinâmicas de transporte mitocondrial alteradas; contudo, tais manifestações não se traduzem em decréscimos globais da biogénese ou da massa destes organelos, pelo que se infere um fenótipo com repercussões predominantemente axonais. Documento ainda a interação intra-axonal da Tctp com duas oncoproteínas anti-apoptóticas da família Bcl-2 – a Mcl1 (do acrónimo inglês, myeloid cell leukemia 1) e a Bcl-XL (Bcl-2-like protein 1) – e aumentos nos níveis de expressão da P53 e da forma ativada da Caspase-3 no cone de crescimento de axónios desprovidos da Tctp. Estes resultados indicam que a Tctp regula o desenvolvimento axonal pela sua ação nos mecanismos de homeostasia celular. O meu estudo sugere, portanto, que à Tctp cabe uma função de fundamental relevância nos mecanismos de formação dos circuitos neuronais em vertebrados.
FCT- SFRH/BD/33891/2009