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Journal articles on the topic "SH3BP2"
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Baquero Forero, Anežka, and Fatima Cvrčková. "SH3Ps—Evolution and Diversity of a Family of Proteins Engaged in Plant Cytokinesis." International Journal of Molecular Sciences 20, no. 22 (2019): 5623. http://dx.doi.org/10.3390/ijms20225623.
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SH3P2 (At4g34660), an Arabidopsis thaliana SH3 and Bin/amphiphysin/Rvs (BAR) domain-containing protein, was reported to have a specific role in cell plate assembly, unlike its paralogs SH3P1 (At1g31440) and SH3P3 (At4g18060). SH3P family members were also predicted to interact with formins—evolutionarily conserved actin nucleators that participate in microtubule organization and in membrane–cytoskeleton interactions. To trace the origin of functional specialization of plant SH3Ps, we performed phylogenetic analysis of SH3P sequences from selected plant lineages. SH3Ps are present in charophytes, liverworts, mosses, lycophytes, gymnosperms, and angiosperms, but not in volvocal algae, suggesting association of these proteins with phragmoplast-, but not phycoplast-based cell division. Separation of three SH3P clades, represented by SH3P1, SH3P2, and SH3P3 of A. thaliana, appears to be a seed plant synapomorphy. In the yeast two hybrid system, Arabidopsis SH3P3, but not SH3P2, binds the FH1 and FH2 domains of the formin FH5 (At5g54650), known to participate in cytokinesis, while an opposite binding specificity was found for the dynamin homolog DRP1A (At5g42080), confirming earlier findings. This suggests that the cytokinetic role of SH3P2 is not due to its interaction with FH5. Possible determinants of interaction specificity of SH3P2 and SH3P3 were identified bioinformatically.
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Nagasu, Akiko, Tomoyuki Mukai, Masanori Iseki, et al. "Sh3bp2 Gain-Of-Function Mutation Ameliorates Lupus Phenotypes in B6.MRL-Faslpr Mice." Cells 8, no. 5 (2019): 402. http://dx.doi.org/10.3390/cells8050402.
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SH3 domain-binding protein 2 (SH3BP2) is an adaptor protein that is predominantly expressed in immune cells, and it regulates intracellular signaling. We had previously reported that a gain-of-function mutation in SH3BP2 exacerbates inflammation and bone loss in murine arthritis models. Here, we explored the involvement of SH3BP2 in a lupus model. Sh3bp2 gain-of-function (P416R knock-in; Sh3bp2KI/+) mice and lupus-prone B6.MRL-Faslpr mice were crossed to yield double-mutant (Sh3bp2KI/+Faslpr/lpr) mice. We monitored survival rates and proteinuria up to 48 weeks of age and assessed renal damage and serum anti-double-stranded DNA antibody levels. Additionally, we analyzed B and T cell subsets in lymphoid tissues by flow cytometry and determined the expression of apoptosis-related molecules in lymph nodes. Sh3bp2 gain-of-function mutation alleviated the poor survival rate, proteinuria, and glomerulosclerosis and significantly reduced serum anti-dsDNA antibody levels in Sh3bp2KI/+Faslpr/lpr mice. Additionally, B220+CD4−CD8− T cell population in lymph nodes was decreased in Sh3bp2KI/+Faslpr/lpr mice, which is possibly associated with the observed increase in cleaved caspase-3 and tumor necrosis factor levels. Sh3bp2 gain-of-function mutation ameliorated clinical and immunological phenotypes in lupus-prone mice. Our findings offer better insight into the unique immunopathological roles of SH3BP2 in autoimmune diseases.
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Shan, Yubao, Xiaoling He, Zi Wang, et al. "Structural Investigations on the SH3b Domains of Clostridium perfringens Autolysin through NMR Spectroscopy and Structure Simulation Enlighten the Cell Wall Binding Function." Molecules 26, no. 18 (2021): 5716. http://dx.doi.org/10.3390/molecules26185716.
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Clostridium perfringens autolysin (CpAcp) is a peptidoglycan hydrolase associated with cell separation, division, and growth. It consists of a signal peptide, ten SH3b domains, and a catalytic domain. The structure and function mechanisms of the ten SH3bs related to cell wall peptidoglycan binding remain unclear. Here, the structures of CpAcp SH3bs were studied through NMR spectroscopy and structural simulation. The NMR structure of SH3b6 was determined at first, which adopts a typical β-barrel fold and has three potential ligand-binding pockets. The largest pocket containing eight conserved residues was suggested to bind with peptide ligand in a novel model. The structures of the other nine SH3bs were subsequently predicted to have a fold similar to SH3b6. Their ligand pockets are largely similar to those of SH3b6, although with varied size and morphology, except that SH3b1/2 display a third pocket markedly different from those in other SH3bs. Thus, it was supposed that SH3b3-10 possess similar ligand-binding ability, while SH3b1/2 have a different specificity and additional binding site for ligand. As an entirety, ten SH3bs confer a capacity for alternatively binding to various peptidoglycan sites in the cell wall. This study presents an initial insight into the structure and potential function of CpAcp SH3bs.
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Kawahara, Kyoko, Tomoyuki Mukai, Masanori Iseki, et al. "SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus." International Journal of Molecular Sciences 22, no. 8 (2021): 4169. http://dx.doi.org/10.3390/ijms22084169.
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Background: The adaptor protein Src homology 3 domain-binding protein 2 (SH3BP2) is widely expressed in immune cells. It controls intracellular signaling pathways. The present study was undertaken to investigate the role of SH3BP2 in a murine systemic lupus erythematosus model. Methods: For the lupus model, we used Faslpr/lpr mice. Clinical and immunological phenotypes were compared between Faslpr/lpr and SH3BP2-deficient Faslpr/lpr mice. Splenomegaly and renal involvement were assessed. Lymphocyte subsets in the spleen were analyzed by flow cytometry. To examine the role of SH3BP2 in specific cells, B cell-specific SH3BP2-deficient lupus mice were analyzed; T cells and bone marrow-derived dendritic cells and macrophages were analyzed in vitro. Results: SH3BP2 deficiency significantly reduced lupus-like phenotypes, presented as splenomegaly, renal involvement, elevated serum anti-dsDNA antibody, and increased splenic B220+CD4−CD8− T cells. Notably, SH3BP2 deficiency in B cells did not rescue the lupus-like phenotypes. Furthermore, SH3BP2 deficiency did not substantially affect the characteristics of T cells and macrophages in vitro. Interestingly, SH3BP2 deficiency suppressed the differentiation of dendritic cells in vitro and reduced the number of dendritic cells in the spleen of the lupus-prone mice. Conclusions: SH3BP2 deficiency ameliorated lupus-like manifestations. Modulating SH3BP2 expression could thus provide a novel therapeutic approach to autoimmune diseases.
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Mukai, Tomoyuki, Shunichi Fujita, and Yoshitaka Morita. "Tankyrase (PARP5) Inhibition Induces Bone Loss through Accumulation of Its Substrate SH3BP2." Cells 8, no. 2 (2019): 195. http://dx.doi.org/10.3390/cells8020195.
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There is considerable interest in tankyrase because of its potential use in cancer therapy. Tankyrase catalyzes the ADP-ribosylation of a variety of target proteins and regulates various cellular processes. The anti-cancer effects of tankyrase inhibitors are mainly due to their suppression of Wnt signaling and inhibition of telomerase activity, which are mediated by AXIN and TRF1 stabilization, respectively. In this review, we describe the underappreciated effects of another substrate, SH3 domain-binding protein 2 (SH3BP2). Specifically, SH3BP2 is an adaptor protein that regulates intracellular signaling pathways. Additionally, in the human genetic disorder cherubism, the gain-of-function mutations in SH3BP2 enhance osteoclastogenesis. The pharmacological inhibition of tankyrase in mice induces bone loss through the accumulation of SH3BP2 and the subsequent increase in osteoclast formation. These findings reveal the novel functions of tankyrase influencing bone homeostasis, and imply that tankyrase inhibitor treatments in a clinical setting may be associated with adverse effects on bone mass.
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Imai, Yoshimichi, Kiyoshi Kanno, Takuya Moriya, et al. "A Missense Mutation in the SH3BP2 Gene on Chromosome 4p16.3 Found in a Case of Nonfamilial Cherubism." Cleft Palate-Craniofacial Journal 40, no. 6 (2003): 632–38. http://dx.doi.org/10.1597/1545-1569_2003_040_0632_ammits_2.0.co_2.
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Objective Cherubism is a rare hereditary multilocular cystic disease of the jaws, characterized by its typical appearance. Although nonfamilial cases have been reported, it is difficult to distinguish nonfamilial cherubism from central giant cell granuloma. Recent studies have revealed the point mutations in the SH3BP2 gene on chromosome 4p16.3 in cherubism families. In this article, the SH3BP2 gene in nonfamilial cherubism was examined. Patient A 21-year-old Japanese woman with nonfamilial cherubism. Interventions Genomic DNA was purified from a blood sample obtained from the patient and used for direct sequencing. In addition, a sample of the lesion, resected during surgery, was used for histologic and immunohistochemical purposes. Results Genomic DNA sequencing found a Pro418Arg mutation in the SH3BP2 gene of the patient. In a histochemical analysis, the multinucleated giant cells proved to be strongly positive for PGM-1, KP-1, and tartrate-resistant acid phosphatase and faintly positive for osteopontin. Conclusions The missense mutation Pro418Arg was identified in the SH3BP2 gene from a nonfamilial case of cherubism. DNA diagnosis may play a significant role in the identification of cherubism.
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Lietman, Steven A., Lihong Yin та Michael A. Levine. "SH3BP2 mutations potentiate osteoclastogenesis via PLCγ". Journal of Orthopaedic Research 28, № 11 (2010): 1425–30. http://dx.doi.org/10.1002/jor.21164.
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Kawamoto, Teruya, Chun Fan, Robert J. Gaivin, Michael A. Levine, and Steven A. Lietman. "Decreased SH3BP2 inhibits osteoclast differentiation and function." Journal of Orthopaedic Research 29, no. 10 (2011): 1521–27. http://dx.doi.org/10.1002/jor.21408.
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Kittaka, Mizuho, Tetsuya Yoshimoto, Henry Hoffman, Marcus Evan Levitan, and Yasuyoshi Ueki. "RANKL-independent osteoclastogenesis in the SH3BP2 cherubism mice." Bone Reports 12 (June 2020): 100258. http://dx.doi.org/10.1016/j.bonr.2020.100258.
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Fan, Chun, Robert J. Gaivin, Thomas A. Marth, Belinda Willard, Michael A. Levine, and Steven A. Lietman. "Cloning and characterization of the human SH3BP2 promoter." Biochemical and Biophysical Research Communications 425, no. 1 (2012): 25–32. http://dx.doi.org/10.1016/j.bbrc.2012.07.043.
Full textDissertations / Theses on the topic "SH3BP2"
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Moon, Cheol. "Rôle de l'adaptateur 3BP2 SH3BP2 dans l'activation des lymphocytes." Nice, 2007. http://www.theses.fr/2007NICE4017.
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Lymphocyte antigen receptor engagement triggers activation of various signaling cascades, initiated by sequential activation of the Src and Syk families of protein tyrosine kinases, and leading to gene transcription. Although they lack both enzymatic and transcriptional activity, adaptor proteins are crucial for this process. The cytoplasmic adaptor protein 3BP2 contains a PH domain, proline–rich regions, and a SH2 domain, and interacts with Syk kinases, the LAT adaptor and the PLCg. 3BP2 plays a positive role in NK cytotoxicity, in basophilic degranulation, and activation of NFAT and AP-1 transcription factors leading to interleukine-2 gene transcription in T cells. Finally, point mutations in 3bp2 gene leads to cherubism, a human pathology related to bone development. 3BP2 thus seems to have an important function in hematopoietic cells. In order to better understand its role in lymphocytes, we looked for and identified novel 3BP2 interacting partners. Among those are essential proteins for lymphocyte signaling like HIP-55 and CIN85 and nucleotidic exchange factors Vav1 and Vav2. We showed that 3BP2 interacts with SH3 domain of HIP-55 or CIN85 by the different proline rich domains, and that the interaction is required for endocytosis and regulation of actin. Moreover, our data indicate that the basal interaction between 3BP2 and Vav family members, mediated by the first proline-rich domain of 3BP2 and a SH3 domain of Vav, is reinforced in a phosphotyrosine-dependent way upon immunoreceptors stimulation in T and B cells. We show that there is a functional cooperation between 3BP2 and Vav family members in small GTPase Rac and NFAT transcription activation in lymphocytes. Finally, a differential exression of 3BP3 is observed in Th1 type lymphocytes. And also, the retroviral overexpression of 3BP2 in primary T lymphocytes accelerates the Th1 type cytokines synthesis and the activation induced cell death. These results suggest 3BP2’s implication in T lymphocyte differentiation and its role in the regulation of cell survival. These results suggest that 3BP2 allows the formation of various multimolecular complexes, and might take part in the regulation of different signaling pathway activated in lymphocytes during immune response<br>L’engagement des récepteurs à l’antigène des lymphocytes déclenche l’activation de différentes cascades de signalisation, initiées par l’activation séquentielle des protéines tyrosine kinases des familles Src et Syk, et aboutissant à la transcription de gènes. Les protéines adaptatrices, pourtant dépourvues d’activité enzymatique ou transcriptionnelle, sont cruciales dans ce processus. La protéine adaptatrice cytoplasmique 3BP2 est constituée d’un domaine PH, de régions riches en proline et d’un domaine SH2, et interagit avec les protéines kinases Syk, l’adaptateur LAT et la PLCg. 3BP2 joue un rôle positif dans la cytotoxicité des cellules NK, dans la dégranulation des mastocytes, et dans l’activation des facteurs de transcription NFAT et AP-1 conduisant à la transcription du gène de l’interleukine-2 dans les cellules T. Enfin, des mutations ponctuelles dans le gène 3bp2 sont à l’origine de la pathologie humaine du chérubisme qui a trait au développement osseux. 3BP2 semble donc posséder une fonction importante dans les cellules du système hématopoïétique. Afin de mieux comprendre son rôle dans les lymphocytes, nous avons recherché et identifié de nouveaux partenaires d’interaction de 3BP2. Parmi ceux-ci se trouvent des protéines essentielles pour la signalisation lymphocytaire comme les protéines HIP-55 et CIN85 et les facteurs d’échange nucléotidiques Vav1 et Vav2. Nous avons montré que 3BP2 interagit directement avec le domaine SH3 de CIN85 ou de HIP-55, qui sont impliqués dans l’endocytose et la régulation d’actine, par les différents domaines riches en proline. D’autre part, nos travaux indiquent que l’interaction basale entre 3BP2 et les membres de la famille Vav, médiée par le premier domaine riche en proline de 3BP2 et un domaine SH3 de Vav, est renforcée de façon phosphotyrosine-dépendante après stimulation des immunorécepteurs des cellules T et B. Cette interaction physique se double d’une interaction fonctionnelle, puisque nous avons montré que 3BP2 coopère avec les membres de la famille Vav pour activer la petite GTPase Rac, la transcription de NFAT dans les lymphocytes. Enfin, une expression différentielle de 3BP2 dans les lymphocytes de type Th1 a été observée. Par ailleurs, la surexpression rétrovirale de 3BP2 dans les lymphocytes T primaires accélère la synthèse des cytokines de type Th1, la mort cellulaire induite par l’activation. Ces résultats suggèrent une implication de 3BP2 au cours de différenciation de lymphocyte T et un rôle dans la régulation de la survie. Ces résultats indiquent que 3BP2, via l’assemblage d’édifices multimoléculaires variés, participe à la régulation des voies de signalisation des lymphocytes pour la réponse immune
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Guezguez, Amel. "Rôle de la protéine adaptatrice 3BP2/SH3BP2 dans la régulation de l'homéostasie osseuse." Nice, 2011. http://www.theses.fr/2009NICE4121.
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Les ostéoclastes sont des cellules multinucléées capables de résorber le tissu osseux, elles se différencient à partir de la lignée hématopoïétique en présence de Receptor Activator of Nuclear Factor NF-kB (RANK-L) et M-CSF (Macrophage-Colony Stimulating Factor). Les récepteurs RANK et M-CSFR relaient et amplifient le signal de leurs ligands en activant de multiples voies de signalisation intracellulaire dont l’intégration aboutira à l’intégration de NFATc1, facteur de transcription essentiel pour la différenciation des ostéoclastes. Les protéines adaptatrices, du fait de leur structure, jouent un rôle crucial dans cette signalisation. De nombreuses études ont montré que la protéine adaptatrice 3BP2/ SH3BP2, initialement identifiée comme une protéine interagissant avec la kinase c-Abl puis comme partenaire des kinases de la famille Src et Syk, joue un rôle important dans la signalisation et l’activation des leucocytes. Des études génétiques ont montré que des mutations du gène 3bp2 chez l’homme sont associées à une dysplasie osseuse génétique « Chérubinisme » et à un phénotype ostéopénique inflammatoire chez la souris. Ces observations laissent entrevoir un rôle additionnel de 3BP2 dans la régulation des cellules du système osseux et particulièrement la différenciation des ostéoclastes. Dans le but d’étudier le rôle de 3BP2 dans la différenciation des ostéoclastes, nous avons utilisé la lignée RAW264. 7, une lignée myélo-monocytaire murine capable de se différencier en ostéoclaste en présence de RANK-L. Avec la méthode d’interférence ARN, nous avons développé des modèles cellulaires « perte de fonction » n’exprimant plus 3BP2. Ces modèles nous ont permis de montrer que l’expression de 3BP2 est essentielle pour la différenciation des ostéoclastes et que son absence altère la différenciation de ces cellules en ostéoclastes. Nous avons ainsi montré que l’effet de l’absence de 3BP2 est restreint à la voie de signalisation RANK sans aucune conséquence sur la voie de signalisation GM-CSF et la différenciation des cellules dendritiques. Dans un premier temps, nous avons montré que cet effet « perte de fonction » est lié à un défaut de polymérisation d’actine et d’activation de la protéine tyrosine kinase Src et des voies de signalisation MAPKs (MEK, ERK, JNK) contrôlées par RANK-L. Nous avons observé également une inhibition de l’induction de NFATc1 et AP-1, des facteurs de transcription essentiels à la différenciation des ostéoclastes. Par la suite, l’analyse transcriptionnelle de différentes protéines impliquées dans la différenciation des ostéoclastes (CaR, TRAP, Cathépsine K) a révélée une inhibition significative de leur induction dans les cellules déficients en 3BP2. Nous avons finalement montré que la reconstruction avec des molécules Src et NFATc1 constitutivement actives restaure la différenciation des ostéoclastes dans les cellules déficients en 3BP2. En conclusion, notre étude a montré que la protéine 3BP2, via la protéine tyrosine kinase Src, joue un rôle central au cours de la différenciation des ostéoclastes en contrôlant les voies de signalisation RANK, impliquées dans l’activation de NFATc1, facteur de transcription clé de la différenciation ostéoclastique<br>Osteoclasts are multinucleated bone-resorbing cells, which derived from hematopoietic cells of the monocyte/macrophage lineage following stimulation with two essential cytokines, RANK-L and M-CSF. The molecular pathways involved in osteoclast formation involve complex network of signaling molecules, including adaptor proteins kinases, which ultimately lead to the activation of a transcriptional program in which NFATc1 plays a pivotal role. The adaptor protein 3BP2, originally identified as a c-Abl binding protein, and a partner of Src and Syk kinases families, has been involved in leucocytes signaling and activation? Genetic studies have further associated mutations of the 3BP2 gene of the human bone disease Cherubism and to inflammation and bone dysfunction in mouse. However, how wild-type 3BP2 exactly functions in osteoclast differentiation has yet been elucidated. In this study, we have investigated the role of endogenous 3BP2 exactly functions in osteoclast differentiation using siRNA-mediated silencing of 3BP2 expression in the RAW264. 7 monocyte/macrophage cell line. We show here that 3BP2 was required for RANK-L-induced differentiation of RAW264. 7 cells was associated with reduced RANK-L-induced actin reorganization and Src, ERK, JNK, IKKα/β, but not p38 phosphorylation. Following RANK-L stimulation, the 3BP2-deficient cells exhibited impaired up-regulation of Src, c-fos and NFATC1 mRNA expression, whereas NFATc2 and NFATc3messengers were not significantly affected. Compared to control cells, 3BP2-knockdown cells induced to osteoclast by RANK-L displayed no up-regulation of Src and NFATc1 proteins? In addition, the introduction of constitutively active mutants of Src and NAFTc1 in 3NP2 deficient cells restored osteoclast differentiation. Finally, we provide evidence that enhanced osteoclast differentiation triggered by a 3BP2 Cherubism mutant also required NFAT activity in RAW264. 7 cells. Together, this study demonstrates that 3BP2 is a key regulator of RANK-mediated osteoclastogenesis through Src and NFATc1 activation
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Kadlub, Natacha. "Tumeurs des maxillaires avec anomalies du développement : à partir des modèles de tumeurs kératokystiques odontogènes et du chérubinisme." Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015PA05T045/document.
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Afin de mieux comprendre les bases physiopathologiques des tumeurs osseuses des mâchoires, nous avons étudié deux modèles de tumeurs associées à des mutations génétiques connues : la tumeur kératokystique odontogène (TKO), liée à la mutation de PTCH1, et le chérubinisme, lié à la mutation de SH3BP2. Au regard des travaux d’oncogénétique, nous formulons l’hypothèse que le développement des tumeurs ostéolytiques bénignes des mâchoires de l’enfant et leur agressivité repose sur un mécanisme génétique. Nous avons montré que la présence d’une mutation de PTCH1 (germinale avec syndrome de Gorlin) dans les TKO était un facteur de mauvais pronostic, stimulant un centre tumoral secondaire, responsable de lésions à distance, mais que cette agressivité pouvait aussi être liée à des mécanismes inflammatoires. Dans le chérubinisme, nous avons montré que la mutation était responsable du phénotype, mais que le type de mutation n’influençait pas le pronostic ni l’agressivité. L’agressivité tumorale est liée au phénotype des cellules géantes multinucléées (cellules myéloïdes à différenciation macrophagique ou ostéoclastique). Nous avons montré, que le modèle murin ne pouvait pas s’appliquer à la pathologie humaine, avec notamment un rôle très secondaire du TNF-α. Enfin nous avons démontré le rôle important de NFATc1 dans la physiopathologie du chérubinisme qui nous a permis de proposer, le tacrolimus, comme le premier agent thérapeutique efficace. Nos résultats suggèrent que les mutations induisent la pathologie et que les changements du microenvironnement (liés à la flore buccale ou à l’éruption dentaire) entretiennent la pathologie<br>To determine pathophysiological bases of jawbone tumors, we studied two genetic models of jawbone tumors: keratocystic odontogenic tumors (KOT) associated to PTCH1 mutation and cherubism associated to SH3BP2 mutation. From oncogenetic theory, we postulate that genetic background controls the development of benign children jawbone tumors. From our work, we demonstrated that PTCH1 mutation (germline mutation in Gorlin syndrome) was an unfavorable prognosis factor for KOT, leading to distant and independent daughter tumors. Moreover, we showed, that chorionic inflammation was associated with a high recurrence rate. In cherubism, SH3BP2 mutation produced cherubism phenotype, but the type of mutation did not affect the aggressiveness of the disease. Cherubism aggressiveness was determined by the phenotype of giant multinucleated cells (whether osteoclasts or macrophages). Furthermore, we showed that murine model could not be transposed to human pathology; indeed it appeared that TNF- α did not play a critical role in human cherubism. On the other side, we showed that NFATc1 played a crucial role in cherubism pathophysiology; this observation allowed us to propose, the tacrolimus, as an effective treatment for this disease. Our results suggest that genetic background induced tumor development, and that microenvironment changes (due to flora of the oral cavity and to teeth eruptions) are responsible to the maintenance and the progression of the disease
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Schickel, Jean-Nicolas. "Lupus érythémateux disséminé et sous-expression de Carabin et Sh3kbp1 : étude par génomique fonctionnelle." Strasbourg, 2011. https://publication-theses.unistra.fr/public/theses_doctorat/2011/SCHICKEL_Jean-Nicolas_2011_ED414.pdf.
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Le lupus érythémateux disséminé (LED) est une maladie autoimmune sévère, caractérisée par la production d’autoanticorps responsables de lésions multiviscérales, et dont l’étiologie est en partie génétique. Les lymphocytes B (LB) jouent un rôle central dans la maladie. Notre analyse du transcriptome des LB de patients lupiques quiescents, en comparaison à des contrôles, a permis d’établir une liste de gènes candidats sous-exprimés ou surexprimés, sur des critères biologiques ou statistiques. Ce projet de thèse propose d’explorer, en utilisant une approche de génomique fonctionnelle, les effets de la sous-expression de deux de ces gènes candidats (Carabin et Sh3kbp1) sur la fonction des LB et le développement d’une autoimmunité chez la souris. Pour cela nous avons produit une lignée de LB et des modèles murins sous-exprimant Carabin ou Sh3kbp1 et étudié leur phénotype. Nos résultats mettent en évidence que Carabin joue le rôle de régulateur négatif des lymphocytes B, et que sa sous-expression (ou son abolition totale) provoque une hypersensibilité du lymphocyte B, qui se caractérise notamment par une accélération de la phosphorylation de Erk après stimulation de la voie du BCR. De plus, Carabin contrôle la cinétique de la réponse lymphocytaire B après immunisation in vivo : en effet, cette réponse est accélérée en absence de Carabin, après immunisation avec un antigène T-dépendant ou T-indépendant. Enfin, Carabin semble jouer un rôle important dans le maintien de la tolérance des lymphocytes B dans le cas d’une stimulation simultanée des voies du BCR et du TLR9. Ceci est illustré par le fait que les souris Carabin KO développent des signes d’autoimmunité après immunisation avec de l’ADN hypométhylé de type CpG. Le deuxième gène étudié est Sh3kbp1. Nous avons montré, dans des cellules B A20 sh3kbp1 knock down, que l’activation du BCR conduit à une accélération des voies Erk et Akt. Ainsi, il semble que les voies de signalisation du BCR soient finement régulées par Sh3kbp1. Ce projet de thèse a permis d’identifier deux gènes dont la sous-expression a une conséquence directe sur la fonction des LB, et peut favoriser l’émergence d’une autoimmunité (dans le cas de Carabin). Ces résultats ouvrent des perspectives très intéressantes quant à l’étude de ces deux gènes en tant que nouveaux gènes de susceptibilité du LED<br>(Carabin) and SH3KBP1. The aim of this thesis project was to precise the consequences of Carabin and Sh3kbp1 underexpression in B cell function and in the development of autoimmunity. To address those issues, we produced: 1/ Carabin and Sh3kbp1 knock-down (KD) B cells and studied their phenotype; 2) a knock-out (KO) and conditional KO of Carabin in B cells or in mature B or T cells. Our results show that Carabin deficiency leads to an increase in T and B cell activation after TCR and BCR stimulation, respectively. Moreover Carabin KO mice and B cell conditional KO mice shows an accelerated T-dependant and T-independent antigen-specific B cell response in vivo. Finally, Carabin KO mice develop signs of autoimmunity after CpG treatment characterized by sustained production of anti-DNA IgG as well as an important deposition of IgG in renal glomeruli. Altogether these results define a new role for Carabin as a negative regulator of B cell signaling that points out a new defective biological pathway in autoimmunity. For Sh3kbp1, we show an acceleration of Erk and Akt phosphorylation in Sh3kbp1 KD B cells after BCR engagement, showing a role for Sh3kbp1 as a negative regulator of B cell receptor signaling. In conclusion, we have identified two genes that are deregulated in B cells during SLE. A deficiency in one of these two genes speed up the B cells response and predispose for the development of autoimmunity in vivo. Further experiments could potentially identify these two genes as new susceptibility genes in SLE
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Connert, Sabine. "Biochemical and genetic analysis of the adaptor protein SH3P7 insights from a newly generated knockout mouse /." [S.l. : s.n.], 2003. http://www.freidok.uni-freiburg.de/volltexte/724.
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Bouhanik, Saadallah. "Caractérisation fonctionnelle de SH3AP1 : un nouvel adaptateur moléculaire." Thèse, 2004. http://hdl.handle.net/1866/15530.
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Chen, Chih-Yang, and 陳志洋. "Structure – Dependent explicit Integration Method with Numerical Dissipation." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/sh3672.
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碩士<br>國立臺北科技大學<br>土木與防災研究所<br>100<br>The step-by-step integration is the most frequently adopted way to obtain the dynamic responses of complex nonlinear structure system. The major topic of this study is to develop a new integration method which can have computational efficiency, unconditional stability, and favorable numerical dissipation, which can accurately integrate the low frequency modes while it can effectively filter out the spurious participation of high frequency modes. Some numerical examples and actual pseudodynamic tests were conducted to confirm the numerical properties of the proposed integration method, especially the characteristics of favorable numerical dissipation.
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王立琦. "Research On Eyewitness Photo Line-Up Identification Procedure During Police Investigation Stage." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/sh3b4e.
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碩士<br>中央警察大學<br>刑事警察研究所<br>106<br>In criminal justice system, eyewitness identification plays an important role not only in investigation stage, but also in both prosecution and conviction in the court. Since the police started investigating crimes and went to the trial stage, the result of eyewitness identification has always been valued by prosecutor and judge. Observed from the police investigation stage, eyewitness identification procedures are mostly conducted during the police investigation stage. This research explores the photo line-up procedure of the United Kingdom and the United States through literature review. Interviewing with six police officers who experienced in conducting photo line-up procedure in practice work through semi-structured interviews. To understand the way of Taiwan police when operating photo line-up identification, and provide the advices of photo line-up procedure for the future.This research indicated four findings. First, it is found that there is no specific clarification between “testify” and “identification”. Second, in the rule of photo line-up identification in Taiwan, that” do not choose the filler and suspect’s photo that too similar with each other”, do not fit the needs of practice. Third, the validity of single identification should be considered more seriously. Fourth, the United Kingdom and the United States attach great importance to sequential photo lineup, making it feasible for legislation in Taiwan. Based on the conclusions of this study, clarifying the definitions of "identification" and "indicating" at the current rule and holding the workshop for the police are important. Also, regularizing sequential Photo Lineup and increasing the rule of “identification” are necessary.
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Jenkins, Meredith L. "Structural and biochemical investigation of the regulation of Rab11a by the guanine nucleotide exchange factors SH3BP5 and TRAPPII." Thesis, 2019. http://hdl.handle.net/1828/11343.
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Rab11 is a critical GTPase involved in the regulation of membrane trafficking in the endocytic pathway, and it’s misregulation is involved in a variety of human diseases including Huntington’s disease and Alzheimer’s disease. Additionally, de novo mutations (DNMs) of Rab11 have been identified in patients with developmental disorders, and interestingly several parasites, viruses, and bacteria can subvert membrane trafficking through Rab11 positive vesicles to allow for replication and evasion from the immune system. Although Rab11 is one of the best characterized Rab GTPases, hindering the capability to completely understand Rab11 regulation and its role in human disease is the lack of detail describing how Rab11 proteins are activated by their cognate guanine nucleotide exchange factors (GEFs). This thesis is therefore focused on revealing the molecular mechanisms of the GEFs responsible for the activation of Rab11: SH3BP5 and TRAPPII. To investigate the recently discovered GEF SH3BP5, we solved the 3.1Å structure of Rab11 bound to SH3BP5 and revealed a coiled coil architecture of SH3BP5 that mediates exchange through a unique Rab-GEF interaction. The structure revealed a unique rearrangement of the switch-I region of Rab11 compared to other solved Rab-GEF structures, with a constrained conformation when bound to SH3BP5. Mutational analysis of switch-I revealed the molecular determinants that allow for Rab11 selectivity over evolutionarily similar Rab GTPases, and GEF deficient mutants of SH3BP5 show greatly decreased Rab11 activation in cellular assays of active Rab11. To interrogate the highly controversial GEF TRAPPII, we recombinantly expressed and purified the 9 subunit, 427 kDa complex in Spodoptera frugiperda 9(Sf9) cells. We found that the TRAPPII complex is a GEF for both Rab1 and Rab11, and we discovered novel activity for another Rab GTPase. To interrogate the role of these GEFs in human disease, we used HDX-MS and nucleotide exchange assays to show that some DNMs destabilize Rab11 either through a complete or partial disruption of nucleotide binding. Importantly, we discovered that one of these DNMs, K13N, completely prevented SH3BP5 and TRAPPII mediated nucleotide exchange, revealing a putative mechanism of disease. Overall the work completed in this thesis leads to a greater understanding of the molecular mechanisms underlying the activation of Rab11 by its cognate GEFs.<br>Graduate<br>2020-11-25
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Zucker, Isaac Jake. "Exploring promoter silencing and re-expression of SH3GL2/endophilin A1 in urothelial cancer." Thesis, 2018. https://hdl.handle.net/2144/30904.
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INTRODUCTION: Bladder cancer (BC) is highly prevalent. It presents as either non-muscle invasive or muscle-invasive disease. The prognosis of muscle invasive disease is poor, with a 5-year survival rate of less than 50%. Treatment approaches for both types of BC have not advanced much in the last few years and new therapies are needed to overcome the large burden of BC. Recently, a large effort has been undertaken to classify BC into molecular subtypes. These analyses have revealed significant alterations in epigenetic modifiers in BC. A previous study from our group revealed that SH3GL2, a negative regulator of receptor tyrosine kinase (RTK) signaling, was lost with high frequency in BC, leading to increased growth of tumor cells in-vitro and in-vivo. Conversely, forced expression of SH3GL2 in BC cell lines attenuated oncogenic behaviors including growth and migration. In addition to genomic deletion, SH3GL2 is subject to methylation-induced silencing, a key epigenetic mechanism.
OBJECTIVE: Epigenetic mechanisms of gene regulation are known to be perturbed in BC. The objectives of this study were to investigate methylation of the SH3GL2 promoter and to test whether agents that promote Deoxyribonucleic acid (DNA) demethylation could be used to re-express SH3GL2 thereby restoring regulation of RTK signaling.
METHODS: Methylation of a specific CpG island in the SH3GL2 promoter was analyzed using methylation-specific Polymerase Chain Reaction (PCR) in a panel of BC cell lines with known SH3GL2 messenger Ribonucleic Acid (mRNA) status. Selected BC cell lines were treated with a variety of demethylating agents at different doses and for different times to evoke the re-expression of silenced SH3GL2. Demethylation inhibitors were combined with the histone deacetylase inhibitor, trichostatin A (TSA), to determine whether further re-expression could be achieved.
RESULTS: The SH3GL2 promoter displayed differing extents of promoter methylation among cell lines examined. In RT4 cells, the only cell line with detectable expression of SH3GL2 mRNA and protein, the promoter was completely unmethylated. In contrast, T24 and 253J cells displayed significant promoter methylation with little to no SH3GL2 mRNA expressed, consistent with methylation-induced silencing. Treatment of T24 and 253J with 5-Aza-2’-deoxycytidine (5-Aza-dC, 20 M), a DNA methyltransferase (DNMT) inhibitor increased gene expression but this was not dose- or time-dependent. Two additional DNMT inhibitors, Zebularine and RG-108 were also tested. A much higher dosage of Zebularine was required to trigger activation (500 M) while RG-108 was unable to trigger gene reactivation at all. Combination treatment with 5-Aza-dC and TSA further increased SH3GL2 expression compared to either agent alone. These results suggest that DNA methyltransferase inhibition is an effective treatment to re-express SH3GL2 in cells with SH3GL2 promoter silencing.
CONCLUSION: The present study shows silencing of SH3GL2 in a variety of BC cell lines as a consequence of DNA promoter hypermethylation. Treatment with demethylating agents was able to increase gene expression. Based on prior findings showing attenuation of tumor cell growth and migration with forced expression of SH3GL2, DNA methyltransferase inhibition represents an effective strategy to re-express SH3GL2 in BC and normalize tumor cell behavior.<br>2020-07-03T00:00:00Z
Book chapters on the topic "SH3BP2"
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"SH3BP2." In Encyclopedia of Medical Immunology. Springer New York, 2020. http://dx.doi.org/10.1007/978-1-4614-8678-7_300329.
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"SH3P9." In Encyclopedia of Cancer. Springer Berlin Heidelberg, 2016. http://dx.doi.org/10.1007/978-3-662-46875-3_102095.
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"SH3P9." In Encyclopedia of Cancer. Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/978-3-642-16483-5_5290.
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Shelah, Saharon. "Existentially closed locally finite groups (Sh312)." In Beyond First Order Model Theory. Chapman and Hall/CRC, 2017. http://dx.doi.org/10.1201/9781315368078-9.
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Ortutay, Csaba, Beston F. Nore, Mauno Vihinen, and C. I. Edvard Smith. "Phylogeny of Tec Family Kinases: Identification of a Premetazoan Origin of Btk, Bmx, Itk, Tec, Txk, and the Btk Regulator SH3BP5." In Advances in Genetics. Elsevier, 2008. http://dx.doi.org/10.1016/s0065-2660(08)00803-1.
Full textConference papers on the topic "SH3BP2"
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Majumdar, Shyama, Edward Gong, Dolores Di Vizio, et al. "Abstract 4066: Loss of Sh3gl2/endophilin A1 is an early event in urothelial carcinoma that regulates malignant behavior." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-4066.
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Apreleva, Sofia V., David F. Wilson, and Sergei A. Vinogradov. "Tomographic Imaging of Oxygen in Tissue by Phosphorescence Lifetime: A Computational Study." In Biomedical Topical Meeting. OSA, 2006. http://dx.doi.org/10.1364/bio.2006.sh32.
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