Rozprawy doktorskie na temat „Sp1”
Kliknij ten link, aby zobaczyć inne rodzaje publikacji na ten temat: Sp1.
Utwórz poprawne odniesienie w stylach APA, MLA, Chicago, Harvard i wielu innych
Sprawdź 50 najlepszych rozpraw doktorskich naukowych na temat „Sp1”.
Przycisk „Dodaj do bibliografii” jest dostępny obok każdej pracy w bibliografii. Użyj go – a my automatycznie utworzymy odniesienie bibliograficzne do wybranej pracy w stylu cytowania, którego potrzebujesz: APA, MLA, Harvard, Chicago, Vancouver itp.
Możesz również pobrać pełny tekst publikacji naukowej w formacie „.pdf” i przeczytać adnotację do pracy online, jeśli odpowiednie parametry są dostępne w metadanych.
Przeglądaj rozprawy doktorskie z różnych dziedzin i twórz odpowiednie bibliografie.
1
Tuthill, Matthew Charles. "N-myc oncogene expression in neuroblastoma is dependent on Sp1 and Sp3". Thesis, University of Hawaii at Manoa, 2003. http://hdl.handle.net/10125/987.
Pełny tekst źródłaStreszczenie:
Regulation of N-myc oncogene expression is an important determinant of the
biological behavior of neuroblastoma. The N-myc promoter contains several potential
binding sites for transcription factors of the Sp1 family. Mutation of a CT-box motif
contained within a 26 base pair region required for N-myc downregulation by retinoic
acid decreased basal transcriptional activity and altered DNA-protein interactions of the
promoter, while mutations flanking this motif did neither. On gel shift this region
generated 3 specific DNA-protein complexes that were reliant on wild type sequence of
the core CT element within it. Both Spl and Sp3 bound to the wild type probe as distinct
complexes in specifically retarded bands, while neither protein was present on mutated
sequences. Lysates from Drosophila S2 cells expressing exogenous Sp1 and Sp3
proteins were able to reproduce the gel shift complexes seen with neuroblastoma nuclear
extract. Transient transfections of S2 cells showed that individually or together, Sp1 and
Sp3 were able to trans-activate a N-myc CT-box-containing luciferase reporter construct
in a dose-dependent manner. Conversely, transfection of CT-box oligonucleotide was
able to decrease endogenous N-myc expression in neuroblastoma cells. Together these
results suggest that the CT-box element serves a critical functional role, and in the basal
state allows for N-myc transactivation by Spl and Sp3.
2
Kim, KyoungHyun. "Domain analysis for estrogen receptor/Sp1-mediated transactivation and detection of estrogen receptor/Sp1 protein interactions in living cells". Texas A&M University, 2004. http://hdl.handle.net/1969.1/2666.
Pełny tekst źródłaStreszczenie:
Estrogen Receptor ? (ER?)/Sp1 activation of GC-rich gene promoters in breast cancer cells is dependent, in part, on the activation function 1 (AF1) of ER?. This study investigates contributions of the DNA binding domain (C) and AF2 (DEF) regions of ER? on activation of ER?/Sp1. 17Beta-estradiol (E2) and the antiestrogens 4-hydroxytamoxifen and ICI 182,780 induced reporter gene activity in MCF-7 and MDA-MB-231 cells cotransfected with human or mouse ER? (hER? or MOR), but not ER? and GC-rich constructs containing three tandem Sp1 binding sites (pSp13) or other E2-responsive GC-rich promoters. Estrogen and antiestrogen activation of hER?/Sp1 was dependent on overlapping and different regions of the C, D, E, and F domains of ER?. Antiestrogen-induced activation of hER?/Sp1 was lost using hER? mutants deleted in zinc finger 1 (amino acids (aa) 185-205), zinc finger 2 (aa 218-245), and the hinge/helix 1 (aa 265-330) domains. In contrast with antiestrogens, E2-dependent activation of hER?/Sp1 required the C-terminal F domain (aa 579-595), which contains a ?-strand structural motif. Moreover, in peptide competition experiments overexpression of NR-box peptides inhibits E2-induced luciferase activity of pERE3, which contains three tandem repeats of consensus ERE sites, whereas E2-induced hER?/Sp1 action was not inhibited by NR-box peptide expression. In contrast, overexpression of a C-terminal (aa 575-595) F domain peptide specifically blocked E2-dependent activation of hER?/Sp1, but not on activation of pERE3, suggesting that F domain interactions with nuclear cofactors are specifically required for ER?/Sp1 action.
Furthermore, direct physical interactions between hER? and Sp1 protein in vivo have been investigated by using Fluorescence Resonance Energy Transfer (FRET) microscopy and image analysis. Consistent with results from transient transfection assay, E2, 4OHT, and ICI enhanced hER?/Sp1 interactions in living cells and these interactions were also confirmed by coimmunoprecipitation. In addition, endogenous hER?/Sp1 action was evaluated by using si RNA for Sp1 and a significant decrease in ligand-induced hER?/Sp1 action was observed after decreased Sp1 expression.
3
Menderin, Nathan. "Studies on the Human Sp1 DNA-Binding Domain". Thesis, University of Exeter, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.507135.
Pełny tekst źródła
4
Andrade, João Nilton Barreto. "O SP1 (transcription factor Sp1) participa da regulação transcricional do Slc2a4 mediada pelo receptor de estrógeno ER-alfa em adipócitos 3T3-L1". Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/5/5160/tde-17082018-095039/.
Pełny tekst źródłaStreszczenie:
O diabetes mellitus tipo 2 (DM2) é caracterizado pela presença de resistência à insulina, a qual pode ser modulada pelo estrógeno, tanto em fêmeas como em machos. Nesse processo, o transportador de glicose GLUT4 (gene Slc2a4, solute carrier family 2 member 4) desempenha papel importante, pois aumento da expressão do GLUT4 melhora o controle glicêmico. Estradiol (E2) regula a expressão do Slc2a4 por meio do balanço dos efeitos contrários de seus receptores (ERs): ER-alfa estimula e ER-beta inibe a expressão. Efeitos transcricionais dos ERs envolvem a participação de co-reguladores, destacadamente o SP1 (transcription factor Sp1), potente estimulador do Slc2a4. Entretanto, o papel do SP1 na regulação do Slc2a4 mediada pelos ERs é desconhecido; e este foi o objetivo do presente estudo. Investigou-se adipócitos maduros 3T3-L1, tratados por 24 horas com E2, agonista de ER-alfa (PPT) ou agonista de ER-beta (DPN). Avaliou-se: a expressão gênica (RT-qPCR) de Slc2a4 e Sp1; o conteúdo (Western blotting) total de GLUT4 e o nuclear de ER-alfa/beta e SP1; a atividade de ligação do SP1 no Slc2a4 (ensaio de mobilidade eletroforética); e a formação de complexos SP1/ER-alfa (imunoprecipitação). Os resultados confirmaram que E2 aumenta a expressão de Slc2a4/GLUT4 pela ação preponderante do ER-alfa. O agonista PPT aumentou: o conteúdo nuclear de SP1, a interação SP1/ER-alfa e a atividade de ligação do SP1 no Slc2a4. O agonista DPN indicou que a ação repressora do ER-beta não envolve o SP1. Conclui-se que o efeito estimulador do ER-alfa na expressão do Slc2a4 envolve mecanismo de transativação gênica via SP1. Essas observações colocam a cooperação ER-alfa/SP1 como um novo alvo para o desenvolvimento de medidas terapêuticas para resistência à insulina e diabetes mellitus tipo 2Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, which can be modulated by estrogen in both females and males. In this process, the glucose transporter GLUT4 (solute carrier family 2 member 4 gene - Slc2a4) plays an important role, since increasing GLUT4 expression improves glycemic control. Estradiol (E2) regulates the expression of Slc2a4, by a mechanism in which estrogen receptors (ERs) play opposite effects: ER-alpha stimulates, whereas ER-beta inhibits the expression. Transcriptional effects of ERs involve co-regulators, notably the transcription factor SP1, a powerful enhancer of Slc2a4. However, the role of SP1 in the ERs-mediated regulation of Slc2a4 is unknown; and that was the aim of the present study. Differentiated adipocytes 3T3-L1 were treated (24 hours) with E2, ER-alpha agonist (PPT) or ER-beta agonist (DPN). It was analyzed: gene expression (RT-qPCR) of Slc2a4 and Sp1; total content o GLUT4 and nuclear content of ER-alpha/beta and SP1 (Western blotting); binding activity of SP1 into Slc2a4 promoter (electrophoretic mobility shift assay); and content of nuclear SP1/ER-alpha complexes (immunoprecipitation). Results confirmed that E2 increases the expression of Slc2a4/GLUT4, by the dominant effect of ER-alpha. The ER-alpha agonist PPT increased the nuclear content of SP1, the interaction of SP1/ER-alpha, and the binding activity of SP1 into the Slc2a4. The agonist DPN evinced that ER-beta activity does not involve the SP1. In conclusion, the enhancer effect of ER-alpha upon Slc2a4 gene expression involves a transactivation mechanism via SP1. This observation point outs the cooperation of ER-alpha/SP1 as a new target for the development of approaches to treat insulin resistance and T2DM
5
Broad, William. "Elucidating the function of the suppressor of ppi1 locus 2". Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:81cb5fb1-e735-453c-9c4b-332a5aa16b27.
Pełny tekst źródła
6
MURATE, TAKASHI, YOSHINORI NOZAWA, YOSHIKO BANNO, MOTOSHI SUZUKI, TETSUHITO KOJIMA, AKIRA TAKAGI, KAZUMI HAGIWARA i in. "Mutated RAS Induced PLD1 Gene Expression through Increased Sp1 Trascription Factor". Nagoya University School of Medicine, 2009. http://hdl.handle.net/2237/16765.
Pełny tekst źródła
7
Darragh, Molly Rose. "Targeting the active serine protease MT-SP1 for tumor detection in vivo". Diss., Search in ProQuest Dissertations & Theses. UC Only, 2010. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3398875.
Pełny tekst źródła
8
Deniaud, Emmanuelle. "Etude des conséquences fonctionnelles de la surexpression du facteur de transcription Sp1". Phd thesis, Ecole normale supérieure de lyon - ENS LYON, 2008. http://tel.archives-ouvertes.fr/tel-00288383.
Pełny tekst źródłaStreszczenie:
Le facteur de transcription Sp1 régule la transcription de nombreux gènes à partir des sites riches en GC. Mon projet a été d'étudier le rôle de Sp1 dans la régulation de l'apoptose et du cycle cellulaire, qui est encore mal défini à l'heure actuelle. Nous avons montré que la surexpression de Sp1 induit un ralentissement du cycle cellulaire en phase G1 et l'apoptose. L'étude du transcriptome a permis d'identifier les mécanismes qui pourraient être à l'origine du ralentissement du cycle cellulaire : la répression de la cycline D2 et l'induction de p18 et cycline G2. Concernant l'induction de l'apoptose, les mécanismes mis en jeu sont spécifiques du type cellulaire et sont différents de ceux décrits jusqu'à ce jour. De façon inattendue, nos résultats montrent que l'ensemble de ces perturbations cellulaires requièrent la liaison de Sp1 à l'ADN mais pourrait être indépendant de son activité transcriptionnelle.
9
Cain, Henry James. "A study of transcription factors STAT3, SP1 and NFkB in breast cancer". Thesis, University of Newcastle Upon Tyne, 2011. http://hdl.handle.net/10443/1333.
Pełny tekst źródłaStreszczenie:
Background and Aims: Breast cancer is the second most common cause of cancer deaths in women. It is a tumour which has been extensively studied at a molecular level and, compared to other solid tissue tumours, our understanding of its biology is extensive. There are however some patients who are considered to have good prognostic feature of their tumours who go on to die from their disease. Transcription factors are the end point of many cell signalling pathways. They form the link between exogenous hormones and growth factors and DNA transcription. For the purpose of this study 3 different transcription factors have been selected for investigation. STAT3 is activated by various growth factors and cytokines including EGF. It is classified as an oncoprotein as its activation can mediate tumorgenisis in nude mice. STAT3 has been shown to confer resistance to apoptosis in breast cancer cells and it is associated with poor outcome in high risk breast cancers. SP1 is a transcription factor which is essential in the expression and the action of estrogen receptors (ER). It is known to be over expressed in other solid tissue tumours but there has been little work into its role in breast cancer. NFkB is activated in many cell survival settings. It is involved in the transcription of anti-apoptotic genes and also plays a role in cell proliferation, angiogenisis and cell adhesion. It is associated in breast cancers with an over expression of the oncogene Bcl-2. It has not been show to be a marker of prognosis but does appear to identify breast cancers with a poor response to chemotherapy. The aim of this study is to investigate the role of these transcription factors in the behaviour of breast cancers and the outcome of the disease. It will also investigate the affect of EGF and estogen stimulation on STAT3 activation in breast cancer cell lines. Methods: This study consists of 2 elements. Firstly an assessment of transcription factor expression in breast cancer samples and secondly a cell model experiment to investigate the stimulation of STAT3 activation. A cohort of 213 patients who presented to the Queen Elizabeth Hospital with invasive breast cancer in 1999 was selected. Tumour samples from these patients were retrieved and using immunohistochemistry were tested for the expression of STAT3, SP1 and NFkB. These results were then correlated with pathological features of the tumours, tumour receptor status (ER, PR HER2 and EGFR) and outcome of the disease. Two cell lines, MCF7 and SKBr3, were cultured in depleted medium. These cells were then stimulated with estrogen and EGF alone and in combination. Flow-cytometry was then used to quantify the levels of phosphorylated STAT3 in the 2 cell lines over a 3 day time course. The level of phosphorylation was then compared to the control lines to asses the effect of stimulation. Results: 209 breast cancers were successfully analysed for the expression of STAT3, 27% of these cancers expressed nuclear STAT3. The results demonstrated a significant correlation of STAT3 expression with cancers of a high grade (p=<0.001), increasing tumour size (p=0.004), vessel space invasion (p=0.034) and lymph node metastases (p=0.015). STAT3 expression was shown to be significantly correlated to high Nottingham prognostic index (NPI) scores. With regards to receptor status it was show that STAT3 expression was significantly associated with ER negative and PR negative cancers (p=0.003), whereas there was no relationship with HER2 status. The results did show that there was a significant relationship between STAT3 expression and EGFR positive cancers (p=0.007). When disease outcome was investigated it was shown that there was a trend towards improved survival in the STAT3 negative group and a significant relationship between STAT3 expression and disease recurrence at 5 years (p=0.04). SP1 expression was determined in 208 of the cancer samples with 33% of the tumours having strong nuclear staining. There was no significant relationship between SP1 expression and any of the pathological features mentioned. SP1 expression was related to ER positive tumours (p=0.015). Though there was no relationship with 5 year survival it appears that SP1 expression does reduce the risk of late (>2yr) disease recurrence (p=0.005). NFkB was over expressed in 15% of the 208 cancers samples. Again a significant correlation was shown with high grade tumours (p=0.001) and large tumours (p=0.014). NFkB expression was also shown to be more prevalent in ER negative cancers (p=0.006) and EGFR positive tumours (p=0.007). There was no significant relationship between NFkB expression and disease outcome. The cell model results showed that in the EGFR positive ER negative cell line (SKBr3), EGF stimulation resulted in a biphasic response of STAT3 phosphorylation, whereas estrogen had no effect on phosphorylation. In the ER positive MCF7 cells, which express low levels of EGFR, again EGF stimulation resulted in a biphasic response curve. Estrogen stimulation does cause an increase in activation but when estrogen is added to EGF stimulation there is an inhibition of STAT3 phosphorylation. Conclusions: This study has demonstrated that STAT3 and SP1 expression is important in disease outcome in breast cancer patients. Though there are differences in levels of expression, NFkB does not appear to have a role in breast cancer outcome. The cell model has show that EGF stimulation of EGFR positive cell lines results in increased STAT3 activation and also that this effect is inhibited by the addition of estrogen stimulation. These results raise important questions which are discussed in the study and suggest areas for further investigation.
10
Deniaud, Emmanuelle. "Étude des conséquences fonctionnelles de la surexposition du facteur de transcription Sp1". Lyon, École normale supérieure (sciences), 2008. http://www.theses.fr/2008ENSL0455.
Pełny tekst źródła
11
Hoffmann, Christoph [Verfasser], Martin [Akademischer Betreuer] Klingenspor i Bernhard [Akademischer Betreuer] Küster. "A novel SP1/SP3 dependent intronic enhancer governing transcription of the UCP3 gene / Christoph Hoffmann. Gutachter: Bernhard Küster ; Martin Klingenspor. Betreuer: Martin Klingenspor". München : Universitätsbibliothek der TU München, 2014. http://d-nb.info/1064383084/34.
Pełny tekst źródła
12
Wijmeersch, Gaëlle. "Etude de la régulation transcriptionnelle du virus de la leucémie bovine: rôle des facteurs de transcription Sp1/Sp3 et de la méthylation de l'ADN". Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210055.
Pełny tekst źródłaStreszczenie:
Étude de la régulation transcriptionnelle du virus de la leucémie bovine :rôle des facteurs de transcription Sp1/Sp3 et de la méthylation de l’ADNDoctorat en sciences, Spécialisation biologie moléculaire
info:eu-repo/semantics/nonPublished
13
Hibino, Emi. "Physicochemical studies on interaction between intrinsically disordered regions in transcription factors Sp1 and TAF4". 京都大学 (Kyoto University), 2017. http://hdl.handle.net/2433/225524.
Pełny tekst źródła
14
McGuigan, Fiona E. A. "Role of the Sp1 polymorphism of the collagen I alpha 1 gene in osteoporosis". Thesis, University of Aberdeen, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369625.
Pełny tekst źródłaStreszczenie:
The Spl polymorphism of the Collagen I alpha 1 gene has previously been associated with low bone density and increased risk of fracture in a number of clinical studies. In chapter 3 the association with fracture was shown to be driven by the Spl polymorphism rather than other single nucleotide polymorphisms located in and around the collagen I alpha 1 gene. In chapter 4, the relationship between the Spl polymorphism and osteoporotic fracture was determined in a prospective population study of men and women. This study confirmed the association between "s" alleles and fracture and showed that COLIA1 genotyping interacted significantly with bone density measurements to enhance prediction of individuals at risk of osteoporotic fracture. In chapter 5, the "s" allele was found to be associated with body size in a population study of young adults. Although there was no association with BMD, individuals who carried the "s" allele were lighter at birth and this trend continued through adolescence and into young adulthood. This suggests that "s" individuals are at increased risk of osteoporosis from an early age, since body size is, in itself a risk factor for osteoporosis. In chapter 6, the effect of Spl alleles on quantitative ultrasound (QUS) was determined in a young post-menopausal population. It was found that there were no significant genotype related differences in broadband ultrasound attenuation (BUA). In chapter 7, family studies were conducted using the quantitative transmission disequilibrium test (qTDT). This showed evidence of a polygenic effect on BMD at the spine and hip and confirmed evidence of an association between Spl "s" alleles and BMD at the femoral neck. The data suggests that the previous associations of Spl alleles and BMD are genuine and not due to population admixture.
15
Farady, Christopher. "The mechanism of inhibition of antibody-based inhibitors of the serine protease MT-SP1". Diss., Search in ProQuest Dissertations & Theses. UC Only, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3311347.
Pełny tekst źródła
16
Kajita, Yoichiro. "The transcription factor Sp3 regulates the expression of a metastasis-related marker of sarcoma, actin filament-associated protein 1-like 1(AFAP1L1)". Kyoto University, 2013. http://hdl.handle.net/2433/179345.
Pełny tekst źródła
17
Dekoninck, Ann. "Etude de la régulation transcriptionnelle du virus de la leucémie bovine: rôle de la chromatine et des facteurs de transcription PU.1 et Sp1/Sp3". Doctoral thesis, Universite Libre de Bruxelles, 2005. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/211015.
Pełny tekst źródła
18
Kypriotou, Magdalini. "Effets de C-krox, Sp1/Sp3 sur la régulation de l'expression du collagène de type I dans des fibroblastes dermiques humains : relation avec la sclérodermie". Caen, 2005. http://www.theses.fr/2005CAEN2017.
Pełny tekst źródłaStreszczenie:
Le collagène de type I est le composant majeur d'un grand nombre de tissus conjonctifs. Ce collagène fibrillaire est codé par les gènes COL1A1 et COL1A2. Les taux d'expression du collagène de type I sont modifiés au cours de différents processus physiologiques et pathologiques (sclérodermie). Dans ce projet, nous nous sommes intéressés à déterminer les effets des facteurs de transcription Sp1 et Sp3 et hc-Krox sur la régulation de l'expression du collagène de type I, dans des fibroblastes dermiques humains sains et sclérodermiques. Les résultats obtenus montrent que hc-Krox stimule l'expression du collagène de type I au niveau protéique et au niveau des taux d'ARNm COL1A1 et COL1A2, dans les fibroblastes normaux de prépuce de jeunes enfants (FP) et d'adultes (FNA), et sclérodermiques (FS). De plus, hc-Krox augmente l'activité transcriptionnelle du gène COL1A1 par l'intermédiaire de la région promotrice -112/-61 pb dans les FP et les FNA. Hc-Krox se lie au sein de cette région, tout comme les facteurs Sp1/3 et CBF. En outre, Sp3 et Sp1 augmentent la néosynthèse collagénique et les taux d'ARNm COL1A1 dans des FP et des FNA. Par ailleurs, ils accroissent l'activité transcriptionnelle du gène COL1A1 via une région localisée dans -198/+1 pb. Des expériences d'IP suggèrent des interactions possibles entre hc-Krox, Sp1 et Sp3, et de plus, chacun d'entre eux peut augmenter les taux d'ARNm des autres facteurs trans dans des FP et des FNA. L'ensemble de ces résultats propose un mécanisme, selon lequel Sp1/3 et hc-Krox interagissent afin de stimuler l'activité transcriptionnelle du gène COL1A1. De plus, cette étude permettra la mise en place de stratégies thérapeutiques ou cosmétiques contre les réactions fibrotiques et le vieillissement cutané.
19
Fletcher, Sally C. "Regulation of the base excision repair pathway". Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:e3db2385-f9aa-4289-9547-3e37cbeddec9.
Pełny tekst źródłaStreszczenie:
Maintenance of genomic stability is paramount for survival of an organism; failure to repair DNA damage ultimately leads to the accumulation of genetically unstable cells and the onset of different human diseases including cancer. DNA single strand breaks and base oxidation/alkylation are among the most frequent types of DNA damage occurring spontaneously in cells. Base excision repair (BER), which copes with the majority of these lesions, is therefore a fundamental DNA repair system. Accordingly, it is important to understand how BER is regulated, and particularly, how and if BER is affected by the cellular load of DNA damage. Although functions of key BER proteins are well-defined, regulation of their expression is poorly understood. During BER, the protein XRCC1 is particularly important. It functions as a scaffold, stabilising repair complexes at sites of DNA damage thereby promoting efficient DNA repair. As a central coordinator in BER, it is therefore of great interest to understand how expression of XRCC1 is controlled. In this thesis I demonstrate that modulation of XRCC1 expression is mediated by transcription factor Sp1. Importantly, Sp1 is also affected during the DNA damage response, suggesting an indirect mechanism promoting BER modulation in response to the cellular DNA damage load. In fact, I show that, in response to persistent DNA strand breaks, the key DNA damage signalling factor ATM phosphorylates Sp1. This initiates Sp1 degradation, negatively affecting BER. Therefore, this thesis identifies a mechanism involving signalling from ATM that regulates BER in response to persistent DNA damage, which I link to susceptibility to apoptosis and cell elimination. I hypothesise that regulation of DNA repair in response to persistent DNA damage constitutes a mechanism to promote the elimination of potentially pre-cancerous cells that accumulate unrepairable levels of DNA lesions.
20
Profanter, Birgit. "Klonierung, rekombinante Expression und erste Charakterisierung des humanen hodenspezifischen Serinprotease-ähnlichen Proteins T-GPI-SP1". Diss., lmu, 2008. http://nbn-resolving.de/urn:nbn:de:bvb:19-90875.
Pełny tekst źródła
21
Jonsson, Anna. "The Impact of the Neuropeptide Substance P (SP) Fragment SP1-7 on Chronic Neuropathic Pain". Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-241637.
Pełny tekst źródłaStreszczenie:
There is an unmet medical need for the efficient treatment of neuropathic pain, a condition that affects approximately 10% of the population worldwide. Current therapies need to be improved due to the associated side effects and lack of response in many patients. Moreover, neuropathic pain causes great suffering to patients and puts an economical burden on society. The work presented in this thesis addresses SP1-7, (Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH), a major metabolite of the pronociceptive neuropeptide Substance P (SP). SP is released in the spinal cord following a noxious stimulus and binds to the NK1 receptor. In contrast to SP, the degradation fragment SP1-7 is antinociceptive through binding to specific binding sites distinct from the NK1 receptor. The aim of this thesis was to investigate the impact of SP1-7 on neuropathic pain. To understand how SP1-7 exerts its effect, a series of N-truncated forms of the heptapeptide were biologically evaluated. A set of small high-affinity ligands was evaluated in animal models of neuropathic pain. To confirm a clinical relevance the levels of SP1-7 in human neuropathic pain were assessed incerebrospinal fluid (CSF) collected from neuropathic pain patients. The results showed that SP1-7 could alleviate thermal as well as mechanical hypersensitivity in three different animal models of neuropathic pain. C-terminal amidation was connected with increased efficacy. N-terminal truncation of SP1-7 indicated a necessity of five amino acids in order to retain biological effect. One small high-affinity ligand showed a significant anti-allodynic effect. CSF levels of SP1-7 in neuropathic pain patients were lower compared to controls. Taken together, these findings demonstrate that the formation of SP1-7 may be attenuated in neuropathic pain. C-terminal amidation and a majority of its amino acids are necessary for stability and permeability. Clearly, SP1-7 and SP1-7 mimetics with high affinity to the SP1-7 binding site ameliorate neuropathic pain-like behaviors in animal models of neuropathic pain. Overall, the findings presented in this thesis contribute to new knowledge regarding the role of SP1-7 and related analogues and fragments in neuropathic pain. In a future perspective, this could be essential for the development of efficient strategies for managing patients with neuropathic pain.
22
O'Connor, Leigh. "Tissue- and stage-specific roles of the ubiquitously expressed transcription factor Sp1 in haematopoietic development". Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8175/.
Pełny tekst źródłaStreszczenie:
Sp 1 is a ubiquitously expressed transcription factor and regulates a range of genes including housekeeping and tissue-specific genes. Studies using a DNA binding domain (DBD)-deficient Spl have shown that Spl is required for haematopoietic specification. Here, we generated a Spl-DBD deficient ESC line to recapitulate the previous model, as well as a novel Spl null ESC line. Spl knockout cells demonstrated a complete absence ofhaematopoietic differentiation, indicating a crucial role for Sp 1 at the early stages of blood cell specification. In contrast, Sp 1 DBD-deficient cells were able to differentiate to haematopoietic progenitors, but failed to terminally differentiate, suggesting a different mechanism of Sp !-mediated transcriptional regulation in early and later stages. Gene expression analysis in Spl knockout cells indicated a novel role for Spl in ESC differentiation potential and mesoderm formation, while chromatin accessibility profiling revealed changes in chromatin structure in the absence ofSpl. We found Sp3, a close family member ofSpl , is able to compensate for loss ofSpl at most sites, but not at some important genes encoding developmental regulators. This work provides novel insights into the interplay between Sp 1 and Sp3 and furthers our understanding of the function of one of the earliest discovered TFs.
23
Ramon, Olivier. "Activité du facteur de transcription Sp1 et équilibre glucidique : implication des espèces réactives de l'oxygène". Université Joseph Fourier (Grenoble), 2000. http://www.theses.fr/2000GRE18010.
Pełny tekst źródła
24
Hobson, Emma. "Functional analysis of a Sp1 binding site polymorphism in the collagen type α gene (COL1A1)". Thesis, University of Aberdeen, 2002. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU534432.
Pełny tekst źródłaStreszczenie:
The exact role of the COL1A1 first intron in gene transcription has not been characterized. To study its role in bone metabolism I examined a transgenic mouse with a targeted deletion of the col1A1 first intron (col-Int). I measured, by peripheral quantitative computed tomography, bone mineral density (BMD), geometry and predicted biomechanical properties in wild-type, heterozygous col-Int and homozygous col-Int mice. First intron deletion affected bone geometry independently of BMD. Homozygous col-Int bones had significantly reduced cross sectional area and bone mineral content compared with wild-type bones, however there was no significant difference in total BMD between the genotypes. Examination of heterozygous col-Int mice demonstrated that the genotype affects were allele-dose and age dependent. The COL1A1 Spl polymorphism is associated with reduced BMD and an increased fracture risk. The polymorphism is situated in COL1A1 intron 1 within a Spl exacting element. Using electrophoretic mobility shift assays I have shown that the unfavourable "s" allele binds Spl with significantly greater affinity than the "S" allele. A fluorescent semi-nested RT-PCR assay demonstrated that in bone RNA from heterozygous subjects (Ss) the transcript abundance from the "s" allele is 2.5-fold greater than from the "S" allele. I examined the effects of the polymorphism on transcription using a reporter fusion gene construct (pCOL-hGH). The gene consisted of a 2.3 kb promoter, exon 1 and intron 1 from COL1A1 fused to the 3' section of the hGHgene. pCOL-hGH contained the "S" variant of the COL1A1 Spl polymorphism, pCOL-hGH-"s" was created by site directed mutagenesis. The pCOL-hGH variants were transfected into a human osteoblast-like cell line (MG63) and incubated for 48 hours. Transfection efficiency was monitored by co-transfection with a luciferase plasmid (pGL3). pCOL-hGH expression was detected by RT-PCR assays, however transcripts were of too low abundance to be detected by RNA hybridization.
25
Profanter, Birgit. "Klonierung, rekombinante Expression und erste Charakterisierung des humanen hodenspezifischen Serinprotease-ähnlichen Proteins T-GPI-SP1". kostenfrei, 2007. http://edoc.ub.uni-muenchen.de/9087/.
Pełny tekst źródła
26
Jungert, Kerstin. "Untersuchungen zur Bedeutung des Transkriptionsfaktors Sp1 in der TGF-beta-1-vermittelten Progression des Pankreaskarzinoms". [S.l. : s.n.], 2006. http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-55615.
Pełny tekst źródła
27
Zhou, Qin. "The Impact of Substance P (SP) N-Terminal Metabolite SP1-7 in Opioid Tolerance and Withdrawal". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-5174-8/.
Pełny tekst źródła
28
Seitz, Isabell. "Proinflammatorische und prothrombotische Wirkung von MT-SP1/Matriptase über Aktivierung des Protease-aktivierten Rezeptors-2 in Endothelzellen". Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-54450.
Pełny tekst źródła
29
Chadjichristos, Christos. "Effets du transforming growth factor-Béta1 et de l'interleukine-1Béta sur l'expression du collagène de type II chez des chondrocytes articulaires : Implication des facteurs de transcription SP1 et SP3". Caen, 2001. http://www.theses.fr/2001CAEN2050.
Pełny tekst źródłaStreszczenie:
Des altérations de la synthèse des composants de la matrice cartilagineuse, en particulier des collagènes, sont observées lors du processus arthrosique. L'étude des mécanismes moléculaires qui contrôlent l'expression des gènes des collagènes de type II, est donc d'une importance capitale pour la compréhension des mécanismes physiopathologiques des maladies ostéoarticulaires. En se basant d'une part, sur les propriétés des facteurs de croissance et des cytokines présents dans le cartilage et, d'autre part, sur le rôle important joué par le collagène de type II dans l'architecture structurale du tissu, nous avons étudié la régulation de l'expression du gène COL2A1 humain dans les chondrocytes articulaires en primoculture sous l'influence de deux cytokines, le TGF-Béta1 et l'IL-1Béta, qui jouent un rôle primordial dans l'oméostasie de ce tissu. Des expériences de transfection transitoire de primocultures de chondrocytes articulaires de lapin (CAL), avec des plasmides contenant diverses régions du promoteur et/ou du premier intron du gène COL2A1 humain ont montré que le promoteur proximal de 63 pb est le siège de l'inhibition de l'expression de ce gène par les deux cytokines qui, même si elles sont connues pour leurs effets opposés dans la physiopathologie du cartilage, semblent mobiliser des facteurs de transcription identiques. En effet, des expérience de protection par la DNase I et de retardement sur gel ont permis de montrer que le TGF-Béta1, tout comme l'IL-1Béta, exercent leur effet inhibiteur sur l'expression du gène COL2A1 humain, en mettant en jeu la même séquence du promoteur COL2A1 -67/-30 pb incluant le site "Sp1-like n°1" localisé entre -42 et -36 pb.
30
Bair, III Warner B. "The Regulation of Growth Factor Receptors EGFR and IGF-IR and the Growth Factor VEGF by Thioredoxin-1". Diss., The University of Arizona, 2005. http://hdl.handle.net/10150/193665.
Pełny tekst źródłaStreszczenie:
Thioredoxin-1 (Trx-1) is a redox protein that is overexpressed in many tumors where it is associated with tumor growth, inhibited apoptosis and decreased patient survival. Through redox reactions, Trx-1 is able to reduce a number of proteins including transcription factors. Sp1 activation has been implicated in the regulation of many genes involved in cellular growth and survival and its overexpression in certain cancer correlates with decreased patient survival. We demonstrate that Trx-1 is able to activate Sp1 in a redox dependent manner. Trx-1 overexpression increases Sp1 transactivation and DNA binding whereas a redox inactive Trx-1 has no effect on Sp1 DNA binding.Sp1 has been implicated in vascular endothelial growth factor regulation and we have shown that Trx-1 expression results in increased hypoxic VEGF expression and increased tumor permeability in vivo. Trx-1 overexpression results in an increase in VEGF expression that is dependent upon Sp1, as inhibition of Sp1 expression with siRNA prevented the induction of VEGF expression by Trx-1. These results suggest that Trx-1 increases VEGF expression under normoxic conditions through a redox dependent increase in the DNA binding of the Sp1 transcription factor. VEGF regulation by Sp1 could increase angiogenesis in relatively perfused areas contributing to the stimulation of tumor growth by Trx-1.We hypothesized that Trx-1 regulation of Sp1 may be part of the mechanism of Trx-1 induction of cellular growth. Sp1 regulates many genes involved in cellular growth including epidermal growth factor receptor (EGFR) and insulin-like growth factor I receptor (IGF-IR). These two growth factor receptors are important for cellular growth and have been shown to be important therapeutic targets for cancer treatment. We report that treatment with the Trx-1 inhibitor PX-12 results in decreased Sp1 DNA binding as well as decreased Sp1 activation and transactivation of VEGF, EGFR, and IGF-IR. These results indicate that Trx-1 promotes cellular growth and survival, in part, through the redox regulation of Sp1 responsive growth genes EGFR and IGF-IR. Inhibition of Trx-1, via PX-12, results in a decrease in EGFR and IGF-IR expression and suggests a new mechanism by which Trx-1 inhibition is clinically effective for treating cancer.
31
Bloomfield, Kelly Louise, i n/a. "Investigation of the Role of Thioredoxin in the Invasive Phenotype and its Interaction with the Transcription Factor Sp1". Griffith University. School of Biomolecular and Biomedical Science, 2003. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20031021.120018.
Pełny tekst źródłaStreszczenie:
Thioredoxin is a small ubiquitous oxido-reductase found in all species. The highly conserved active site, which facilitates thioredoxins redox activity, contains two redox active cysteine residues. Thioredoxin has numerous protein substrates to which it donates H+ ions and it can also function as a free radical scavenger. Through these activities thioredoxin is able to influence the redox state of not only its protein targets, but also the entire cellular environment. Thioredoxin has been implicated in many biological functions, and one mechanism by which it influences these functions is through interactions with a number of transcription factors including NF-kappa-B and p53. Thioredoxin also has numerous extracellular biological roles. It has been shown that thioredoxin is actively secreted from a number of normal and transformed cell lines including fibroblasts and activated B and T cells. This study investigates the role of thioredoxin in embryonic implantation and cancer cell metastasis, two physiological functions which rely on the same basic processes. Thioredoxin expression has previously been shown to be increased in many cancers. However it has not yet been established whether this increase is a causative or a side effect of the cancerous phenotype. Similarly thioredoxin expression has previously been shown to be increased during different phases of the oestrus cycle and pregnancy. This thesis describes the role of thioredoxin in embryonic implantation using a marmoset model. A thioredoxin cDNA was isolated and subsequently sequenced. Preliminary antibody experiments indicated that the anti human thioredoxin monoclonal antibodies available in our laboratory would recognise marmoset thioredoxin. Subsequently immunocytochemistry using anti human thioredoxin antibodies was carried out on sectioned marmoset uterus and embryonic tissue. The results indicated that thioredoxin is expressed by cells at the embryonic-maternal interface of early implantation sites. Further studies demonstrated that thioredoxin is also expressed and secreted by cultured blastocysts in vitro. This thesis also describes the role of thioredoxin in cancer cell metastasis. Results of this study indicate that thioredoxin is actively involved in facilitating the invasive phenotype of breast cancer cells. The two cell lines utilised were MCF-7, a well differentiated, relatively non-invasive breast cancer cell line; and MDA-MB-231, a poorly differentiated, highly invasive breast cancer cell line. The cell lines were transfected with thioredoxin sense, antisense and 1SS (encodes thioredoxin with both active cysteine residues mutated to serine residues and is thus redox inactive) constructs. The results demonstrate that when endogenous thioredoxin levels are increased, i.e. transfected with a sense thioredoxin construct, the invasive breast cancer cell line MDA-MB-231 becomes more invasive, conversely when endogenous levels are decreased, i.e. transfected with antisense or 1SS constructs, the invasive capacity of these cells decreases. However, when the endogenous level of thioredoxin was manipulated in the relatively non-invasive cell line MCF-7 very little effect was observed. Results also indicate that thioredoxin has the ability to act as a chemoattractant for actively invading breast cancer cells. Both of these functions appear to be dependent on thioredoxin's redox activity. Additional studies described in this thesis have shown that thioredoxin is involved in the regulation of Sp1 in vitro. Sp1 is a transcription factor known to regulate the transcription of a number of genes whose products are intimately involved in the invasive phenotype. The results in this study suggest that Sp1 DNA binding is regulated by thioredoxin such that when reduced by the enzyme its binding to DNA is facilitated. Results also indicate that Sp1 may regulate the transcription of thioredoxin by binding to Sp1 sites within the thioredoxin promoter.
32
Bosso, Matteo [Verfasser]. "Human nuclear PYHIN proteins inhibit LTR-driven gene expression by sequestering the host transcription factor Sp1 / Matteo Bosso". Ulm : Universität Ulm, 2021. http://d-nb.info/1227450737/34.
Pełny tekst źródła
33
Bloomfield, Kelly Louise. "Investigation of the Role of Thioredoxin in the Invasive Phenotype and its Interaction with the Transcription Factor Sp1". Thesis, Griffith University, 2003. http://hdl.handle.net/10072/366170.
Pełny tekst źródłaStreszczenie:
Thioredoxin is a small ubiquitous oxido-reductase found in all species. The highly conserved active site, which facilitates thioredoxins redox activity, contains two redox active cysteine residues. Thioredoxin has numerous protein substrates to which it donates H+ ions and it can also function as a free radical scavenger. Through these activities thioredoxin is able to influence the redox state of not only its protein targets, but also the entire cellular environment. Thioredoxin has been implicated in many biological functions, and one mechanism by which it influences these functions is through interactions with a number of transcription factors including NF-_B and p53. Thioredoxin also has numerous extracellular biological roles. It has been shown that thioredoxin is actively secreted from a number of normal and transformed cell lines including fibroblasts and activated B and T cells. This study investigates the role of thioredoxin in embryonic implantation and cancer cell metastasis, two physiological functions which rely on the same basic processes. Thioredoxin expression has previously been shown to be increased in many cancers. However it has not yet been established whether this increase is a causative or a side effect of the cancerous phenotype. Similarly thioredoxin expression has previously been shown to be increased during different phases of the oestrus cycle and pregnancy. This thesis describes the role of thioredoxin in embryonic implantation using a marmoset model. A thioredoxin cDNA was isolated and subsequently sequenced. Preliminary antibody experiments indicated that the anti human thioredoxin monoclonal antibodies available in our laboratory would recognise marmoset thioredoxin. Subsequently immunocytochemistry using anti human thioredoxin antibodies was carried out on sectioned marmoset uterus and embryonic tissue. The results indicated that thioredoxin is expressed by cells at the embryonic-maternal interface of early implantation sites. Further studies demonstrated that thioredoxin is also expressed and secreted by cultured blastocysts in vitro. This thesis also describes the role of thioredoxin in cancer cell metastasis. Results of this study indicate that thioredoxin is actively involved in facilitating the invasive phenotype of breast cancer cells. The two cell lines utilised were MCF-7, a well differentiated, relatively non-invasive breast cancer cell line; and MDA-MB-231, a poorly differentiated, highly invasive breast cancer cell line. The cell lines were transfected with thioredoxin sense, antisense and 1SS (encodes thioredoxin with both active cysteine residues mutated to serine residues and is thus redox inactive) constructs. The results demonstrate that when endogenous thioredoxin levels are increased, i.e. transfected with a sense thioredoxin construct, the invasive breast cancer cell line MDA-MB-231 becomes more invasive, conversely when endogenous levels are decreased, i.e. transfected with antisense or 1SS constructs, the invasive capacity of these cells decreases. However, when the endogenous level of thioredoxin was manipulated in the relatively non-invasive cell line MCF-7 very little effect was observed. Results also indicate that thioredoxin has the ability to act as a chemoattractant for actively invading breast cancer cells. Both of these functions appear to be dependent on thioredoxin's redox activity. Additional studies described in this thesis have shown that thioredoxin is involved in the regulation of Sp1 in vitro. Sp1 is a transcription factor known to regulate the transcription of a number of genes whose products are intimately involved in the invasive phenotype. The results in this study suggest that Sp1 DNA binding is regulated by thioredoxin such that when reduced by the enzyme its binding to DNA is facilitated. Results also indicate that Sp1 may regulate the transcription of thioredoxin by binding to Sp1 sites within the thioredoxin promoter.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Biomedical Sciences
Full Text
34
Polikandriotis, John Anastasios. "Elucidating the regulation of vascular smooth muscle alpha-actin gene expression in fibroblasts". Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1078857443.
Pełny tekst źródłaStreszczenie:
Thesis (Ph. D.)--Ohio State University, 2004.Title from first page of PDF file. Document formatted into pages; contains xiv, 177 p.; also includes graphics (some col.). Includes bibliographical references (p. 160-177).
35
Manolopoulos, Konstantinos. "Kollagen-1-Alpha-1-Sp1-Polymorphismus, koronare Herzkrankheit und Myokardinfarkt bei Patienten mit und ohne Diabetes mellitus Typ 2". [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=975679821.
Pełny tekst źródła
36
Vicart, Axel. "Modifications post-traductionnelles et activité du facteur de transcription Sp1 au cours de la division cellulaire et de l'apoptose". Aix-Marseille 2, 2006. http://theses.univ-amu.fr.lama.univ-amu.fr/2006AIX22027.pdf.
Pełny tekst źródłaStreszczenie:
La protéine Sp1 est une facteur de transcription eucaryote capable d'activer sélectivement la transcription d'une grande variété de gènes en se fixant, par l'intermédiaire de motifs en doigts de zinc, aux boites GC de l'ADN. Sa spécificité d'action est assurée par de modifications posttraductionnelles multiples et des interactions sélectives avec d'autres protéines régulatrices. Sp1 est ainsi impliqué dans de nombreux processus biologiques et contrôle notamment l'expression de gènes associés à la division cellulaire et à l'apoptose. C'est autour de ces deux axes que ma thèse a été menée. Nous avons dans un premier temps focalisé notre étude sur la déphosphorylation de Sp1 par la phosphatase 2A survenant dans les cellules en prolifération. Nous avons pu démontrer que celle-ci touchait simultanément plusieurs sérines et thréonines et que la forme déphosphorylée de Sp1 était préférentiellement recrutée par la chromatine in vivo. Nous avons par ailleurs cherché à préciser l'implication de Sp1 dans l'activité anti-proliférative et pro-apoptotique des inhibiteurs d'histones deacétylases dans divers types de cellules tumorales. Nous avons montré que la trichostatine A induisait le clivage de Sp1 par les caspases et identifié les sites cibles correspondants. Des résultats préliminaires indiquent que le fragment C-terminal est davantage recruté à la chromatine que la protéine Sp1 entière et exerce une activité transcriptionnelle accrue. Nous avons ainsi décrit deux mécanismes de régulation post-traductionnelle de Sp1 (déphosphorylation et clivage) conduisant à une augmentation de sa fixation in vivo à l'ADN, lors de la division cellulaire et de l'apoptose. Nous proposons dès lors que le recrutement de Sp1 est un pré requis pour l'expression d'un grand nombre de gènes induits dans ces deux contextes, la transcription sélective de chacun d'entre eux étant éclenchée par des mécanismes de régulation complémentairesSp1 is a eukaryotic transcription factor which specifically binds to GC boxes on DNA via its zinc finger domain. Its selective activity on a large panel of genes is ensured by multiple posttranslational modifications and selective interactions with other regulating proteins. Among these genes are those implicated in cell division and apoptosis. My PhD focused on the role of Sp1 in these two processes. We first analyzed the mechanism and function of the phosphatase 2Ameditated dephosphorylation of Sp1 which occurs in proliferating cells. We showed that PP2A simultaneously targets several serines and threonines and that the Sp1 dephosphorylated form is preferentially recruited by chromatin in vivo. In addition, we sought to specify the role of Sp1 in the anti-proliferative and pro-apoptotic activities of histone deacetylases inhibitors in various tumoral cell types. We have shown that trichostatin A induces the cleavage of Sp1 by caspases and identified the corresponding target sites. Preliminary results indicate that the released Cterminal fragment is more recruited onto chromatin than the whole Sp1 protein and that it exerts an increased transcriptional activity. In conclusion, we have described two mechanisms of posttranslational regulation of Sp1 (dephosphorylation and cleavage) which both lead to an increase of its in vivo DNA binding during cell division and apoptosis. We propose that Sp1 recruitment is pre required for the expression of a large number of genes induced in these two processes, while their selective transcription is triggered by complementary regulatory mechanisms
37
Sroka, Isis Calsoyas. "Regulation Of Membrane-Type 1 Matrix Metalloproteinase In Prostate Cancer". Diss., The University of Arizona, 2007. http://hdl.handle.net/10150/194830.
Pełny tekst źródłaStreszczenie:
Membrane type-1 matrix metalloproteinase (MT1-MMP) is a metalloproteinase which becomes upregulated in prostate cancer and has been implicated in processes of prostate cancer metastasis. Here, we show that MT1-MMP is minimally expressed in nonmalignant primary prostate cells, moderately expressed in DU-145 cells, and highly expressed in invasive PC-3 and PC-3N cells. Using MT1-MMP promoter reporters and mobility shift assays, we show that Sp1 regulates MT1-MMP expression in DU-145, PC-3, and PC-3N cells and in PC3-N cells using chromatin immunoprecipitation analysis and silencing RNA. Investigation of signaling pathways in these cells showed that DU-145 cells express constitutively phosphorylated extracellular stress-regulated kinase (ERK), whereas PC-3 and PC-3N cells express constitutively phosphorylated AKT/PKB and c-Jun NH2 terminal kinase (JNK). We show that MT1-MMP and Sp1 levels are decreased in PC-3 and PC-3N cells when PI-3K and JNK are inhibited, and that MT1-MMP levels are decreased in DU-145 cells when MEK is inhibited. Transient transfection of PC-3 and PC-3N cells with a dominant-negative JNK or p85, and DU-145 cells with a dominant negative ERK, reduced MT1-MMP promoter activity. We also identified the insulin-like growth factor (IGF-1R) as an upstream regulatory component of MT1-MMP in PC-3N and LNCaP cells, which express high and low levels of the enzyme, respectively. Treatment of PC-3N cells with an IGF-1R specific inhibitor decreased MT1-MMP promoter activity, RNA and protein levels. Additionally, treatment of LNCaP cells with a synthetic androgen to increase IGF-1R levels and subsequent treatment with IGF-I increased MT1-MMP promoter activity, RNA and protein levels. Analysis of MT1-MMP and IGF-1R expression in human prostate cancer tissues demonstrated that MT1-MMP expression was high in the apical cytoplasmic regions of PIN and prostate cancer and less intense in the basalateral cytoplasmic membrane regions of benign glands. IGF-1R was expressed in normal glands and highly expressed in prostate cancer. In conclusion, we have identified several novel mechanisms regulating MT1-MMP expression in prostate cancer cell lines as well as differential localization of the enzyme in human prostate cancer tissues. These results provide insight into the complex mechanisms of prostate cancer metastasis and may be useful for developing future diagnostic procedures or therapies.
38
Robette, Gwenaelle. "Régulation transcriptionnelle du virus HTLV-1: rôle fonctionnel des sites Sp1 et implication du cofacteur CTIP2 dans la latence virale". Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209294.
Pełny tekst źródłaStreszczenie:
L’infection par le rétrovirus complexe T-lymphotrope HTLV-1 (Human T-cell Leukemia Virus type 1), premier rétrovirus humain découvert, touche de 10 à 20 millions de personnes à travers le monde dans des régions endémiques et induit des désordres lymphoprolifératifs de cellules T. Seulement 5 % des personnes infectées développent, après une longue phase asymptomatique, une maladie dont une forme agressive et rapidement mortelle de leucémie nommée ATLL (Adult T-cell Leukaemia/Lymphoma).L’infection par le virus HTLV-1 se caractérise par l’absence de virémie due à la latence du virus dans la majorité des cellules infectées suite à la répression transcriptionnelle de l’expression virale in vivo. Cette latence favorise très probablement le développement tumoral en permettant aux cellules infectées d’échapper à la réponse immunitaire médiée par l’hôte infecté.
Au cours de ce travail, nous avons tout d’abord identifié deux nouveaux sites de liaison pour le facteur de transcription Sp1, localisés dans la région R du promoteur LTR du HTLV-1. Nous les avons caractérisés physiquement par des expériences de retard de migration sur gel et avons mis en évidence la liaison de Sp1 au niveau de ces deux sites. Nous avons ensuite déterminé l’affinité de Sp1 pour les différents sites du promoteur du HTLV-1 et avons montré que les sites Sp11 (localisé dans la région U3) et Sp15 (localisé dans la région U5) sont les plus forts. Nous avons étudié l’impact de mutations de tous les sites Sp1 du LTRHTLV-1 sur son activité promotrice en conditions basales et transactivées par Tax dans le contexte d’un vecteur rapporteur épisomal. Nous avons mis en évidence que les sites Sp1 de la région R du LTRHTLV-1 agissent comme répresseurs de la transcription du LTR5’ mais n’ont aucun effet sur l’activité promotrice du LTR3’.
Dans une seconde partie de notre travail, nous avons étudié l’implication du cofacteur CTIP2 dans la répression transcriptionnelle du HTLV-1 et avons mis en évidence sa capacité à réprimer la transactivation médiée par Tax des promoteurs (LTR5’ et LTR3’) du HTLV-1 en cellules T-lymphoïdes Jurkat. Nous avons également montré par des expériences d’immunoprécipitation de chromatine, le recrutement de CTIP2 aux promoteurs du HTLV-1 dans une lignée infectée de manière latente par le rétrovirus et son absence dans une lignée productive. A l’inverse, Sp1 est présent dans les deux types de lignées. De plus, nous avons exclus l’implication des sites Sp1 du LTRHTLV-1 dans le recrutement du cofacteur étant donné que CTIP2 réprime toujours la transactivation Tax-dépendante du LTRHTLV-1 muté au niveau de tous les sites Sp1.
Finalement, nous avons étudié l’importance des modifications post-traductionnelles de CTIP2 dans son activité de cofacteur transcriptionnel. Nous avons montré que CTIP2 était acétylé par les HATs CBP et p300 et avons identifié 5 sites majeurs d’acétylation. Nous avons mis en évidence l’importance de l’acétylation de la lysine 604 de CTIP2 dans son activité répressive de la transactivation Tax-dépendante des LTRs du HTLV-1.
L’ensemble de ces résultats suggère un rôle du corépresseur CTIP2 dans la régulation transcriptionnelle du promoteur du HTLV-1 ainsi qu’un rôle répresseur des sites Sp1 de la région R du LTRHTLV-1 dans la transcription des gènes viraux au départ du LTR5’. La poursuite de ce travail devrait contribuer à une meilleure compréhension des mécanismes moléculaires génétiques et épigénétiques impliqués dans la latence et la réactivation transcriptionnelles des promoteurs du HTLV-1.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
39
Gamstätter, Thomas [Verfasser]. "TH17-Zellen und Interleukin-17 in der Genese intraperitonealer Abzesse durch das zwitterionische Polysaccharid Sp1 von Streptococcus pneumoniae / Thomas Gamstätter". Köln : Deutsche Zentralbibliothek für Medizin, 2012. http://d-nb.info/1025433602/34.
Pełny tekst źródła
40
Bernardes, José Miguel Andrade de Oliveira. "Genética da osteoporose pós-menopausica : Estudo dos polimorfismos Sp1 do COLIA 1, PvuII do ERα, FoKI e BsmI do VDR". Master's thesis, Universidade do Porto. Reitoria, 2003. http://hdl.handle.net/10216/9764.
Pełny tekst źródła
41
GHAYOR, CHAFIK. "Regulation de la transcription du gene du collagene de type ii. Implication des facteurs de transcription de la famille sp1". Caen, 2000. http://www.theses.fr/2000CAEN2022.
Pełny tekst źródłaStreszczenie:
L'alteration de la synthese des composants de la matrice cartilagineuse, en particulier le collagene de type ii, est observee au cours du processus arthrosique. Afin d'etudier la regulation transcriptionnelle du gene du collagene de type ii humain (col2a1) dans des chondrocytes articulaires de lapin (cal), des experiences de transfection transitoire ont ete realisees avec des plasmides contenant diverses regions du promoteur et/ou du premier intron de ce gene. Ces experiences nous ont permis de montrer que le gene co2la1 contient, au niveau du premier intron, un amplificateur transcriptionnel specifique. D'autre part, un promoteur de 266 pb semble contenir toutes les sequences necessaires pour l'expression specifique de ce gene dans les chondrocytes. Grace a des experiences de protection par l'adnase i et de retardement sur gel, des sites de liaison specifiques pour les facteurs de transcription sp1 et sp3 ont ete identifies dans le promoteur et le premier intron du gene col2a1. Sp1 active la transcription d'un promoteur de 266 pb du gene col2a1, alors que sp3 n'a pas d'effet sur ce gene, et ceci quel que soit l'etat de differenciation des chondrocytes. De plus, sp3 en se liant aux memes elements cis que sp1, s'oppose a l'effet activateur induit par sp1. Les effets transcriptionnels de ces deux facteurs sur le gene col2a1 se trouvent correles avec le taux proteique des collagenes neosynthetises. Cette etude montre egalement que l'activite de liaison et les taux proteiques de sp1 et sp3 sont specifiquement reduits au cours de la dedifferenciation des chondrocytes, phenomene qui s'accompagne d'une diminution de la synthese du collagene de type ii. Etant donne le profil d'expression de sp1 et sa capacite de se lier specifiquement aux differents elements cis du gene col2a1, nous pensons que ce facteur intervient de maniere importante dans la regulation de l'expression specifique du collagene de type ii, aussi bien dans des conditions physiologiques que pathologiques.
42
Bernardes, José Miguel Andrade de Oliveira. "Genética da osteoporose pós-menopausica : Estudo dos polimorfismos Sp1 do COLIA 1, PvuII do ERα, FoKI e BsmI do VDR". Dissertação, Universidade do Porto. Reitoria, 2003. http://hdl.handle.net/10216/9764.
Pełny tekst źródła
43
Jabet, Carole. "L'expression génique au sein du tissu musculaire squlettique : analyse du complexe multigénique codant les isoformes de chaînes lourdes de myosine humaines : étude des mécanismes de régulation transcriptionnelle du gêne codant l'énolase beta de souris, ex vivo". Châtenay-Malabry, Ecole centrale de Paris, 1996. http://www.theses.fr/1996ECAP0492.
Pełny tekst źródłaStreszczenie:
Les processus de détermination myogénique et de différenciation au sein du tissu musculaire squelettique, peuvent être abordés par l'étude de l'expression de gènes qui codent des protéines de structure comme les isoformes de chaine lourde de myosine (MyHC) ou du métabolisme comme la sous-unité béta de l'énolase (enzyme de la glycolyse), spécifiques de ce tissu. Afin de voir s'il existe une corrélation entre la position des 5 gènes MyHC squelettiques humains groupés sur le chromosome 17 et leur expression temporelle, nous nous sommes intéressés à la régulation transcriptionnelle du gène MyHC embryonnaire. Nous avons aussi étudié la régulation transcriptionnelle du gene de l'enolase beta de souris en culture. Nous avons caracterise un promoteur proximal de 120 paires de bases actif dans les myoblastes et les fibroblastes et inactif dans les myotubes et un amplificateur de 230 paires de bases spécifique du stade myotube, très conservé entre l'homme et la souris, localisé à l'extrémité 3' du premier intron du gène de l'enolase béta. L'activation transcriptionnelle de ce gène dans les myotubes dépend d'interactions multiples entre des facteurs activateurs des familles MEF2 et MYoD, fixés sur l'amplificateur musculaire intronique, et des facteurs transcriptionnels ubiquitaires des familles Nf1 et Sp1, fixés sur le promoteur.
44
Tuthill, Matthew C. "N-myc oncogene expression in neuroblastoma is dependent on Sp1 and Sp3". 2003. http://proquest.umi.com/pqdweb?index=0&did=765961141&SrchMode=1&sid=8&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1209166306&clientId=23440.
Pełny tekst źródła
45
Hang-CheYang i 楊杭哲. "Pin1-mediated Sp1 Highly Phosphorylation by CDK1 Inhibits Sp1 DNA-binding Activity during Mitosis". Thesis, 2016. http://ndltd.ncl.edu.tw/handle/98877159167808789027.
Pełny tekst źródłaStreszczenie:
博士國立成功大學
生物資訊與訊息傳遞研究所
104
Our previous study found that Sp1 phosphorylation at Threonine739 decreased DNA-binding activity of Sp1 during mitosis. Here, we demonstrated that Sp1 Thr739 phosphorylation alone is necessary, but not sufficient for the decrease of DNA-binding activity in mitosis stage. Further study showed that Pin1 could be recruited to phospho-Thr739-Pro740 motif of Sp1 and then regulate the interaction between phospho-Thr739-Sp1 and CDK1 during mitosis, thereby Sp1 could be further highly phosphorylated by CDK1 at Ser720, Thr723, and Thr737. The Pin1-mediated Sp1 highly phosphorylation by CDK1 can decrease DNA-binding affinity of Sp1. Loss of C-terminus (amino acid 741-785) significantly increased the phosphorylation by CDK1 without Pin1, suggesting that C-terminus of Sp1 inhibits highly phosphorylation by CDK1. The structure study by X-ray crystallography indicated that Pin1 increased the cis signal and showed that the phospho-Thr739-Sp1 peptide located in the active site of Pin1, suggesting that Pin1 alters the conformation of C-terminal Sp1. During mitosis, Sp1 highly phosphorylation by CDK1 not only stabilized protein level of Sp1 by reducing the interaction between Sp1 and its ubiquitin E3-ligase RNF4 but also made Sp1 completely leave the chromosomes by decreasing the DNA-binding activity of Sp1. This regulation of Sp1 by CDK1 phosphorylation can facilitate the cell cycle progression. Thus, Pin1-mediated conformational alteration of C-terminal Sp1 is critical for the Sp1 highly phosphorylation by CDK1 in mitosis, leading cell cycle progression. In addition to the cell cycle regulation in cancer cells, highly phosphorylation can preserve Sp1 during cell cycle and then Sp1 can rapidly start to regulate gene transcription in cancer cells after cell division. So we investigated the genes Sp1 regulated in cancer cells to clarify the function of preserved Sp1 during cell cycle. Our ChIP-seq and small RNA-seq data suggested that Sp1 can regulate lots of microRNAs in cancer cells and may affect tumor progression via miRNA regulation. Our data showed that Sp1 can exhibit positive and negative control on miRNA, so we chose the Sp1-positive regulated miR-22 and Sp1-negative regulated miR-103 for our study. In this study, we found that Sp1 can activate the promoter of miR-22 by Sp1 binding site, and Sp1 can repress miR-103 through non-canonical intronic microRNA regulation. Instead of regulating miR-103 host gene promoter, Sp1 can directly regulate miR-103 promoter. Although there is not any Sp1 binding site on miR-103 promoter, we found that Sp1 can repress miR-103 transcription by forming a repression complex with YY1 and HADC1. This study showed that Sp1 can exhibit positive and negative control on miRNA transcription in cancer cells, suggesting that Sp1 might play an important role in tumorigenesis by regulating miRNA.
46
Wobus, Manja, Elke Wandel, Sonja Prohaska, Sven Findeiß, Katrin Tschöp i Gabriela Aust. "Transcriptional regulation of the human CD97 promoter by Sp1/Sp3 in smooth muscle cells". 2008. https://ul.qucosa.de/id/qucosa%3A31891.
Pełny tekst źródłaStreszczenie:
The EGF-TM7 receptor CD97 shows different features of expression and function in muscle cells compared to hematopoetic and tumor cells. Since the molecular function and regulation of CD97 are poorly understood, this study aimed at defining its basal transcriptional regulation in smooth muscle cells (SMCs).
The computational analysis of the CD97 5′-flanking region revealed that the TATA box-lacking promoter possesses several GC-rich regions as putative Sp1/Sp3 binding sites. Transfection studies with serially deleted promoter constructs demonstrated that the minimal promoter fragment resided in the − 218/+ 45 region containing one out of five identified GC-boxes in the leiomyosarcoma cell line SK-LMS-1 and human bronchial smooth muscle cells (HbSMCs). Mutation of the most proximal GC-site in CD97 reporter gene constructs caused a significant decrease in promoter activity. Gel shift assays and chromatin immunoprecipitation revealed that Sp1 and Sp3 bound specifically to the most proximal GC-site. Furthermore, we showed that Sp1 and Sp3 over-expression activates CD97 promoter activity in HEK293 cells.
Our data characterize for the first time the activity of the human CD97 promoter which is controlled by Sp1/Sp3 transcription factors in SMCs.
47
Yi-TingWang i 王怡婷. "The role of sumoylation in Sp1 degradation". Thesis, 2011. http://ndltd.ncl.edu.tw/handle/91410864285894193793.
Pełny tekst źródła
48
Lee, Yi-Chern, i 李易諶. "Role of the Sp1-pVHL- HIF-1 α". Thesis, 2008. http://ndltd.ncl.edu.tw/handle/25cdbe.
Pełny tekst źródłaStreszczenie:
碩士國立中山大學
生物醫學研究所
96
Introduction: Since the era of Marshall, H. pylori has been to be implicated in many upper digestive tract diseases, such as gastritis, peptic ulcer disease, mucosa- associated lymphoid tissue lymphoma, and even gastric adenocarcinoma. In 1994, WHO recognized H. pylori as a definite carcinogen for gastric cancer. Many study had shown that microbial pathogens may induce oxidative stress in infected host cell. And this may also represent an important mechanism leading to epithelial injury in H. pyloric infection. Oxidative stress plays a role in altering epithelial cell turnover, accelerating apoptosis and increasing oxidative DNA damage. One of the evidences for this phenomenon is increasing level of reactive oxygen species (ROS) measured in the mucosa of infected stomach. ROS may activate HIF-11α transcription. HIF-1α overexpression had been detected in several human cancers. Furthermore its overexpression correlates significantly with highly aggressive disease, lymph node metastasis, clinicopathological status and poor prognosis in some cancer types. It may up regulate hypoxia-induced gene, such as the vascular endothelial growth factor (VEGF) transcription and angiogenesis. Therefore we propose Sp1-pVHL-HIF-1α pathway may play a role the carcinogenesis in Hp -associated gastric cancer. Material and methods: We took Paraffin-embedded specimens from 89patients, who had undergone UGI endoscopy and gastric mucosa biopsy. We assessed the Sp1, pVHL, HIF-1α in all cases by immunohistochemistry and then evaluated their correlation with the H pylori infection. Chi-square and Fisher’s exact test was performed to determine the significance of the difference between Sp1, pVHL, HIF-1α. Results: There are not significant difference in nuclear Sp1 expression and H. pylori different (p=0.59). Sp1 expression was not significant, (p=0.91, 0.93, 0.36, 0.42, 0.51) with sex, age, location, TNM stage and cell differentiation. pVHL protein was mainly expressed in the cytoplasm. There are no significant difference with H. pylori infection (p=0.14). The relationship pVHL protein expression between with sex, age, lesion site, TNM stage and cell differentiation were not significant (p=0.39, 0.70, 0.69, 0.83, 0.70). HIF-1α protein was mainly expressed in the nuclei. There are not significant association with H. pylori infection (p=0.49). There were no significant differences between HIF-1α protein expression with sex, age, location, TNM stage and cell differentiation (p=0.94, 0.32, 0.75, 0.35, 0.60). Furthermore, In normal tissue the expression of HIF-1α had significant association with pVHL(p=0.0002), and the expression also had no a mariginally significant association with Sp1(p=0.096). Expression of Sp1 had significant association with pVHL(p=0.0016)in tumor tissue, Therewas a significant association between normal and tumor tissue expression of the pVHL and Sp1(p=0.038, 0.019), but the expression of HIF-1α had no significant(p=0.23). Conclusion: In this study, we attempt to determine the association between Sp1-pVHL -HIF-1α pathway and a role in the carcinogenesis in H. pylori infection. Although we didn’t confirm the hypothesis Sp1-pVHL -HIF-1α pathway playing an critical role in the mechanism of gastric cancer. We concluded that there is no significance between the expression of Sp1, pVHL and HIF-1α and gastric cancer, but the role of this pathway in the Hp infection associated carcinogenesis is still to be clarified.
49
Chen, Jui-Jsen, i 陳瑞楨. "Identification and Characterization of Sp1 interacting protein: TACC3". Thesis, 2006. http://ndltd.ncl.edu.tw/handle/27162152105938668092.
Pełny tekst źródłaStreszczenie:
碩士國立成功大學
藥理學研究所
94
TACC3 was identified as a member of the transforming acidic coiled-coil (TACC) family characterized by their highly homologous carboxyl-terminal acidic coiled-coil domain. This protein has been found to be overexpressed in differentiating cells such as erythroid cells or in fast dividing cells such as cells in testis. One of its most studied biologicalfunctions so far is the stabilization of centrosomal microtubules during M phase. However the mechanism of TACC3 expression during the cell cycle is yet not well understood. Here, we used Thymidine and Nocodazole to synchronize cells at G1/S and G2/M phase respectively, to study TACC3’s gene expression. Both TACCs RNA and protein expression showed a cyclical pattern over cell cycle. The importance of the fluctuations of TACC3 mRNA in the cell cycle raised the question of how it is regulated. Since the TACC3 mRNA stability between interphase and mitosis cells did not differ significantly, thus we proceeded to study the transcriptional regulation. Therefore, about 600 base pairs upstream of the 5’ untranslated region was cloned into pGL2-luciferase reporter vector. Our luciferase activity data showed that this region portrays a cyclical pattern, thus may contain cell cycle dependent regulatory elements. The deletion fragment, we identified two regions that play important role in the basal activity and activation of TACC3 during mitosis contained Sp1 and CDE binding sites. Further experiments will need to be done to confirm whether Sp1 bind to this region and which regulatory elements bind to the CDE binding sites.
50
Tsung-IHsu i 徐宗溢. "The Role of Sp1 in Lung Cancer Progression". Thesis, 2012. http://ndltd.ncl.edu.tw/handle/39606507918669443898.
Pełny tekst źródłaStreszczenie:
博士國立成功大學
基礎醫學研究所
100
Lung cancer is the leading cause of cancer mortality and the prognosis for lung carcinoma patients is generally poor (5-yr survival rate 〈 15%) in Taiwan, even if diagnosed and treated successfully, patients with early stage of lung carcinoma have a 5-year survival rate of only 70% after surgical resection. Understanding of the molecular attributes of lung tumors provides clues to develop the therapy targeting defective cellular pathways for lung cancer, such as Ras proteins which activates Ras/Raf-1/mitogen-activated protein kinase pathway. The transcription factor, specificity protein (Sp) 1 was found to be overexpressed in several human cancers and the Sp1 levels correlated with tumor grade/stage and poor prognosis. The overall objective of this study is to identify the functional role and potential contribution of Sp1 in lung tumorigenesis. In the first section, we showed that the Sp1 level was highly increased and required for lung tumor growth in transgenic mice bearing KrasG12D-induced lung tumors under the control of doxycycline. Furthermore, the Sp1 level was highly upreguated in lung adenocarcinoma cells with low invasiveness and in patients with stage I lung cancer. We also demonstrated that Sp1 was downregulated in lung adenocarcinoma cells with high invasiveness and in patients with stage IV lung adenocarcinoma. In particular, Sp1 expression in highly invasive lung adenocarcinoma cells is still significantly higher than that in normal lung fibroblast. Moreover, Sp1 inversely regulated migration, invasion and metastasis of lung adenocarcinoma cells in vivo. In addition, a decrease in the Sp1 level in highly invasive lung adenocarcinoma cells resulted from instability of the Sp1 protein. Furthermore, overexpression of Sp1 in highly invasive lung adenocarcinoma cells increased expression of E-cadherin, a suppressor of metastasis, and attenuated the translocation of -catenin into the cellular nucleus which leads to tumor malignancy. Taken together, Sp1 level accumulates strongly in early stage and then declines in late stage, which are important for lung cancer cell proliferation and metastasis, respectively, during tumorigenesis. In the second section, we evaluated the effect of an anti-tumor drug, betulinic acid (BA), targeting Sp1 on lung cancer in vitro and in vivo. Herein, we found that BA treatment increased the sumoylation of Sp1 by inhibiting SENP1 expression and the recruitment of E3 ligase, RNF4, followed by resulting in ubiquitination-mediated degradation in a 26S proteosome-dependent pathway. In addition, both of BA and mithramycin A (MMA) treatment inhibited lung tumor growth, and downregulated Sp1 protein expression in KrasG12D-induced lung cancers of bitransgenic mice. In the study of gene expression profiles of KrasG12D-induced lung cancers of bitransgenic mice with and without Sp1 inhibition, 542 of genes were affected by repressing Sp1 expression. One of these important genes, cyclin A2 (CCNA2), was addressed deeply to indicate that CCNA2 expression was attenuated by BA and MMA treatments through decreasing Sp1 protein stability and DNA binding affinity, respectively. Downregulation of CCNA2 led to decrease in Rb phosphorylation and to causing cell cycle G2/M-arrest. BA-mediated cellular Sp1 degradation and antitumor effect were also further confirmed in xenograft mouse model by using H1299 cells. Knock down of Sp1 in lung cancer cells attenuated the anti-cell growth effect of BA. Taken together, this study clarified the mechanism of BA-mediated Sp1 degradation, and identified that Sp1 level plays a pivotal role in BA-induced repression of lung cancer growth.