Nuclear protein in testis (NUT) midline carcinoma is an exceedingly rare subtype of squamous poorly-differentiated carcinoma and is considered one of the most aggressive human solid tumors [1-3]. NUT midline carcinoma is a relatively new entity, that may likely be under-recognized and under-diagnosed. All ages and organs might be affected, but most frequently NUT midline carcinoma arises along the trunk or the head and, in particular, in midline structures such as the mediastinum [1-3]. NUT midline carcinoma is characterized by the pathognomonic chromosomal rearrangement between the NUT gene with either bromodomain-containing protein 4 (BRD4) or, less frequently, with BRD3 (on chromosome 9), leading to the fusion genes BRD4-NUT or BRD3-NUT, respectively [1-3]. BRD is a DNA reader that activates transcription by binding to acetyl-modified lysine residues of histone tails [1, 3, 4]. The expression of several oncogenes, including transcription factors and MYC, is epigenetically regulated by BRD. ...
Image Credit: Good Search I recently received a comment from someone who included some information about Nut Midline Carcinoma. If you are familiar with this aggressive cancer, and want a blog that focuses on it, heres a link. About Nut Midline Carcinoma. http://stridesforstephenstepstocurenmc.wordpress.com/stephensstory/
This article further shows the power of pharmacologic screens in highly characterized human cancer-derived cell lines. Despite lingering concerns about the artificial conditions in which cancer cell lines are established and maintained, it is now clear that major oncogenic pathways are typically faithfully maintained in vitro, and thus clinically relevant associations regarding sensitive histotypes and genomic subsets can be generated from these screens. Here, the investigators show that BET inhibition is a valid therapeutic strategy in a broad range of cancers, extending the potential impact beyond hematologic malignancies and the rare NUT midline carcinomas that have been the focus of prior investigations.. The association of JQ1 sensitivity with MYCN amplification status is compelling for 2 distinct reasons. The obvious one is that it nominates MYCN amplification as a predictive biomarker for BET inhibitory activity in patients, suggesting that diseases such as neuroblastoma, small-cell lung ...
Compare & find the top performing anti-Monkey Cytoplasmic Protein NCK1 antibody for Immunohistochemistry (Paraffin-embedded Sections) (IHC (p)).
Purpose: NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer characterized by rearrangement of the NUT gene. Research advances have provided opportunities for targeted therapy in NMC, yet the clinical features of this rare disease have not been systematically characterized. We report on a large population of such patients to identify the disease characteristics and treatments, correlate them with outcome, and to consider clinical recommendations.. Experimental Design: A clinical database was established using retrospective demographic and outcomes data available on all known cases of NMC. Questionnaires were completed by treating physicians. Pathologic, demographic, and clinical variables were assessed for 63 patients, the largest cohort of patients with NMC studied to date. Outcome data from 54 patients were available for survival analyses.. Results: The diagnosis of NMC has increased annually since 2007. Since 2009, there has been an observed increase in the age at diagnosis ...
R. Kiss, Zhu, M., Jójárt, B., Czajlik, A., Solti, K., Fórizs, B., Nagy, É., Zsila, F., Beke-Somfai, T., and Tóth, G., "Structural features of human DJ-1 in distinct Cys106 oxidative states and their relevance to its loss of function in disease", Biochimica et Biophysica Acta (BBA) - General Subjects, vol. 1861, pp. 2619-2629, 2017. ...
Objective: Rare disease Background: NUT midline carcinoma (NMC) is a rare, highly lethal malignancy that results from a chromosome translocation and mostly arises in the midline organs. To date, no treatment has been established. Most patients receive combinations of chemotherapy regimens and radiation, and occasionally subsequent resection; nevertheless, patients have an average survival hardly exceeding 7 months. Case Report: A 21-year-old patient was admitted to our division with a large mediastinal mass with lung nodules, multiple vertebral metastases, and massive nodal involvement. In a few days, the patient developed a superior vena cava syndrome and an acute respiratory failure. Due to the rapid course of the disease, based on preliminary histology of poorly differentiated carcinoma, a dose-dense biweekly chemotherapy with paclitaxel, ifosfamide, and cisplatin was started. In the meantime, the diagnosis of NMC was confirmed. A surprising clinical benefit was obtained after the first cycle ...
Mice lacking the Axl receptor tyrosine kinase (RTK) and its family members exhibit detrimental effects on their reproductive ability. AXL is localized to Sertoli cells, which are the major nurturing cells in the seminiferous ...
cDNA, FLJ94334, Homo sapiens growth arrest-specific 2 (GAS2), mRNA (Growth arrest-specific 2, isoform CRA_a) contains a PF00307 domain.. cDNA, FLJ94334, Homo sapiens growth arrest-specific 2 (GAS2), mRNA (Growth arrest-specific 2, isoform CRA_a) contains a PF02187 domain.. cDNA, FLJ94334, Homo sapiens growth arrest-specific 2 (GAS2), mRNA (Growth arrest-specific 2, isoform CRA_a) is proteolytically cut by caspase-7 (C14.004) cleavage. SRVD-GKTS.. cDNA, FLJ94334, Homo sapiens growth arrest-specific 2 (GAS2), mRNA (Growth arrest-specific 2, isoform CRA_a) is proteolytically cut by caspase-3 (C14.003) cleavage. SRVD-GKTS.. ...
Cancer is driven, in part, by the interplay of regulatory transcription factors and dynamic alterations in chromatin structure. Previous studies of MYCN-amplified neuroblastoma have focused on the role of MYCN in transcriptional activation and the super-enhancer machinery to drive a neuroblastoma oncogenic program (20, 43, 56, 57). The role of MYCN in repressing tumor suppressor programs in neuroblastoma has not been as well explored. Our genome-scale CRISPR-Cas9 screen revealed a preferential dependency of neuroblastoma cells on the transcriptional silencing machinery of the PRC2 complex. Our mechanistic studies determined that MYCN directly drives the transcriptional repressor EZH2 in neuroblastoma, providing a direct link between MYCN overexpression and the repression of tumor suppressor programs in this disease. Specifically, EZH2 represses a neuronal differentiation program in MYCN-amplified neuroblastoma, enhancing the undifferentiated phenotype characteristic of neuroblastoma. Indeed, ...
Cancer is driven, in part, by the interplay of regulatory transcription factors and dynamic alterations in chromatin structure. Previous studies of MYCN-amplified neuroblastoma have focused on the role of MYCN in transcriptional activation and the super-enhancer machinery to drive a neuroblastoma oncogenic program (20, 43, 56, 57). The role of MYCN in repressing tumor suppressor programs in neuroblastoma has not been as well explored. Our genome-scale CRISPR-Cas9 screen revealed a preferential dependency of neuroblastoma cells on the transcriptional silencing machinery of the PRC2 complex. Our mechanistic studies determined that MYCN directly drives the transcriptional repressor EZH2 in neuroblastoma, providing a direct link between MYCN overexpression and the repression of tumor suppressor programs in this disease. Specifically, EZH2 represses a neuronal differentiation program in MYCN-amplified neuroblastoma, enhancing the undifferentiated phenotype characteristic of neuroblastoma. Indeed, ...
Neuronal migration is a crucial process that allows neurons to reach their correct target location to allow the nervous system to function properly. AP-2α is a transcription factor essential for neural crest cell migration and its mutation results in apoptosis within this cell population, as demonstrated by genetic models. We down-modulated AP-2α expression in GN-11 neurons by RNA interference and observe reduced neuron migration following the activation of a specific genetic programme including the Adhesion Related Kinase (Axl) gene. We prove that Axl is able to coordinate migration per se and by ChIP and promoter analysis we observe that its transcription is directly driven by AP-2α via the binding to one or more functional AP-2α binding sites present in its regulatory region. Analysis of migration in AP-2α null mouse embryo fibroblasts also reveals an essential role for AP-2α in cell movement via the activation of a distinct genetic programme. We show that AP-2α plays an essential role in cell
The KOMP Repository Collection is located at the MMRRC at the University of California, Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
Background-Sprouting angiogenesis is a key process driving blood vessel growth in ischemic tissues and an important drug target in a number of diseases, including wet macular degeneration and wound healing. Endothelial cells forming the sprout must develop front-rear polarity to allow sprout extension. The adaptor proteins Nck1 and 2 are known regulators of cytoskeletal dynamics and polarity, but their function in angiogenesis is poorly understood. Here we show that the Nck adaptors are required for endothelial cell front-rear polarity and migration downstream of the angiogenic growth factors VEGF-A and Slit2. Methods and Results-Mice carrying inducible, endothelial-specific Nck1/2 deletions fail to develop front-rear polarized vessel sprouts and exhibit severe angiogenesis defects in the postnatal retina and during embryonic development. Inactivation of NCK1 and 2 inhibits polarity by preventing Cdc42 and Pak2 activation by VEGF-A and Slit2. Mechanistically, NCK binding to ROBO1 is required for ...
DJ-1 is a conserved, ubiquitous protein associated to a large number of intracellular processes. Human DJ-1 has been linked to several pathologies, including hereditary forms of Parkinsons disease, cancer, and amyotrophic lateral sclerosis. Several cytoprotective functions of DJ-1 have been reported, however, its actual mechanisms of action remain elusive. In vitro, DJ-1 has been shown to bind zinc and copper(II) at its active site, which contains a conserved cysteine (C106), and copper(I) at a different binding site. C106 is essential to DJ-1 function, and is easily oxidized upon oxidative stress. Here, we investigated the metal-binding- and redox properties of DJ-1 in living human cells by in-cell NMR. Intracellular DJ-1 is surprisingly free from interactions with any other cellular components and as such is clearly detectable by NMR. Metal-bound forms of DJ-1 were not observed upon treating the cells with excess zinc or copper. No copper binding was observed when co-expressing DJ-1 with the ...
NUT midline carcinoma (NMC) is an aggressive type of squamous cell carcinoma that is defined by the presence of BRD-NUT fusion oncogenes, which encode chimeric proteins that block differentiation and maintain tumor growth. BRD-NUT oncoproteins contain two bromodomains whose binding to acetylated histones is required for the blockade of differentiation in NMC, but the mechanisms by which BRD-NUT act remain uncertain. Here we provide evidence that MYC is a key downstream target of BRD4-NUT. Expression profiling of NMCs show that the set of genes whose expression is maintained by BRD4-NUT is highly enriched for MYC upregulated genes, and MYC and BRD4-NUT protein expression is strongly correlated in primary NMCs. More directly, we find that BRD4-NUT associates with the MYC promoter and is displaced by acetyl histone mimetic BET inhibitor, JQ1, which prevents binding of BET bromodomains to acetylated histones. BRD4-NUT is also required to maintain MYC expression in NMC cell lines, as shown by a ...
Impaired apoptosis is involved in the pathogenesis of cancer, and triggering this process in tumor cells is an important target of therapy (52 , 53) . Advanced-stage, MYCN-amplified neuroblastoma are often resistant to conventional chemotherapeutic drugs because of aberrations/dysfunctions in their apoptotic machinery (22, 23, 24, 25) , making the search for novel agents capable of inducing programmed cell death in this type of tumor mandatory. The data presented in this paper provide the first evidence that the synthetic flavone, flavopiridol, causes apoptosis in neuroblastoma cell lines derived from metastatic, MYCN-amplified, stage IV tumors.. Flavopiridol activity against a variety of tumor types, both in vitro and in vivo in experimental xenografts, is well documented (26, 27, 28, 29, 30, 31, 32, 33 , 39 , 41) , and recent findings have reported promising therapeutic results of this agent in patients with refractory neoplasms (36, 37, 38) . To our knowledge, studies of flavopiridol ...
The Ets-Related Gene (ERG) belongs to the Ets family of transcription factors and is critically important for maintenance of the hematopoietic stem cell population. A chromosomal translocation observed in the majority of human prostate cancers leads to the aberrant overexpression of ERG. We have identified regions flanking the ERG Ets domain responsible for autoinhibition of DNA binding and solved crystal structures of uninhibited, autoinhibited, and DNA-bound ERG. NMR-based measurements of backbone dynamics show that uninhibited ERG undergoes substantial dynamics on the millisecond-to-microsecond timescale but autoinhibited and DNA-bound ERG do not. We propose a mechanism whereby the allosteric basis of ERG autoinhibition is mediated predominantly by the regulation of Ets-domain dynamics with only modest structural changes. Structural and dynamic studies of the transcription factor ERG reveal DNA binding is allosterically autoinhibited.,Regan MC, Horanyi PS, Pryor EE Jr, Sarver JL, Cafiso DS, ...
High-quality Axl proteins from ACROBiosystems. Various species and tags of Axl proteins. Minimal Batch-to-Batch Variation. Bulks in stock.
Looking for online definition of AXL receptor tyrosine kinase in the Medical Dictionary? AXL receptor tyrosine kinase explanation free. What is AXL receptor tyrosine kinase? Meaning of AXL receptor tyrosine kinase medical term. What does AXL receptor tyrosine kinase mean?
The human neutrophil lipocalin (HNL), a member of the large family of lipocalins that exhibit various physiological functions, is coexpressed in granulocytes with progelatinase B (MMP-9). Part of it is covalently bound to the proenzyme and therefore may play a possible role in the activation process: of promatrix metalloproteinases. We now report that HNL is able to accelerate the direct activation of promatrix metalloproteinases slightly. A significant enhancement of the activity could be demonstrated for the HgCl2- and the plasma kallikrein-induced activation of all three secretory forms of proMMP-9 and of proMMP-8. The same activating effects were exerted by HNL isolated from granulocytes as well as by the recombinant forms expressed by the yeast Pichia pastoris or by Escherichia coli. This demonstrates that the carbohydrate moiety is not essential for the biological activity of HNL. Activation and activity enhancement are obviously mediated by entrapping the remaining N-terminal sequence ...
Multiple proof-of-principle experiments suggest that targeting members of the Myc family of oncoproteins will have significant therapeutic benefit in human tumors. Deregulated expression of MYCN, one of the three family members implicated in human tumors, is prevalent in both pediatric and adult neuroendocrine tumors. We have shown previously that MYCN-amplified neuroblastoma cells depend on high levels of Aurora-A expression for maintaining N-Myc function. Similarly, Aurora-A and N-Myc bind each other and together drive an oncogenic gene expression program in neuroendocrine prostate tumors. Although stabilization of N-Myc does not require the catalytic activity of Aurora-A, we found that two inhibitors of Aurora-A disrupt the Aurora-A/N-Myc complex and promote degradation of N-Myc via the Fbxw7 ubiquitin ligase. Disruption of the Aurora-A/N-Myc complex inhibits N-Myc-dependent transcription, correlating with tumor regression and prolonged survival in a mouse model of MYCN-driven neuroblastoma, ...
Growth arrest-specific 6, also known as GAS6, is a human gene coding for the Gas6 protein. It is similar to the Protein S with the same domain organization and 43% amino acid identity. It was originally found as a gene upregulated by growth arrested fibroblasts. Gas6 is a gamma-carboxyglutamic acid (Gla) domain-containing protein thought to be involved in the stimulation of cell proliferation. Gas6 has been shown to interact with AXL receptor tyrosine kinase, MerTK and TYRO3. The presence of Gla needs a vitamin K-dependent enzymatic reaction that carboxylates the gamma carbon of certain glutamic residues of the protein during its production in the endoplasmic reticulum. GRCh38: Ensembl release 89: ENSG00000183087 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000031451 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". "Entrez Gene: GAS6 growth arrest-specific 6". Mark MR, Chen J, Hammonds RG, Sadick M, Godowsk PJ (Apr 1996). "Characterization of Gas6, a member ...
Effect of Single Amino Acid Substitution on Oxidative Modifications of the Parkinsons Disease-Related Protein, DJ-1 Mutations in the gene encoding DJ-1 have been identified in patients with familial Parkinsons disease (PD) and are thought to inactivate a neuroprotective function. Oxidation of the sulfhydryl group to a sulfinic acid on cysteine residue C106 of DJ-1 yields the "2O " form, a variant of the protein with enhanced neuroprotective function. We hypothesized that some familial mutations disrupt DJ-1 activity by interfering with conversion of the protein to the 2O form. To address this hypothesis, we developed a novel quantitative mass spectrometry approach to measure relative changes in oxidation at specific sites in mutant DJ-1 as compared with the wild-type protein. Treatment of recombinant wild-type DJ-1 with a 10-fold molar excess of H2O2 resulted in a robust oxidation of C106 to the sulfinic acid, whereas this modification was not detected in a sample of the familial PD mutant ...
Regulation of BRD4 function and cancer: BRD4 is an epigenetic reader that plays a central role in transcriptional regulation, cellular growth control, and cell cycle progression. Dysregulation of BRD4 function has been implicated in the pathogenesis of a large number of cancers including acute myeloid leukemia, multiple myeloma, Burkitts lymphoma, diffuse large B cell lymphoma, breast cancer, colon cancer, and ovarian carcinoma. BRD4 is also the target of translocation t(15;19), which results in the formation of BRD4-NUT fusion oncogene that accounts for the highly lethal transforming activity of NUT midline carcinoma (NMC). Although BRD4 has emerged as a key cancer therapeutic target, the mechanisms that regulate BRD4 function have not been elucidated. How alteration of BRD4 function leads to cancer also remains largely unknown. We reported that BRD4 preferentially occupies pluripotency genes in embryonic and cancer stem cells to regulate their transcription. Others also showed that BRD4 ...
Mammalian Nck1 and Nck2 are closely related adaptor proteins that possess three SH3 domains, followed by an SH2 domain, and are implicated in coupling phosphotyrosine signals to polypeptides that regulate the actin cytoskeleton. However, the in vivo functions of Nck1 and Nck2 have not been defined. We have mutated the murine Nck1 and Nck2 genes and incorporated β-galactosidase reporters into the mutant loci. In mouse embryos, the two Nck genes have broad and overlapping expression patterns. They are functionally redundant in the sense that mice deficient for either Nck1 or Nck2 are viable, whereas inactivation of both Nck1 and Nck2 results in profound defects in mesoderm-derived notochord and embryonic lethality at embryonic day 9.5. Fibroblast cell lines derived from Nck1−/− Nck2−/− embryos have defects in cell motility and in the organization of the lamellipodial actin network. These data suggest that the Nck SH2/SH3 adaptors have important functions in the development of mesodermal ...
In this study, we have adopted a proteomic approach to characterize new ligands of the TCR‐signaling ITAM motifs. In this way, we identified the GPCR‐interacting protein β‐Arr1 as a novel direct ligand of the TCR that is recruited to unphosphorylated ITAMs in a manner dependent on TCR triggering. While β‐Arr1 was previously described as a cytoplasmic effector of both GPCRs and RTKs (Hupfeld & Olefsky, 2007), this is the first demonstration of β‐Arr1 binding to the TCR, a multi‐subunit receptor without intrinsic enzymatic activity. We found that β‐Arr1 recruitment to the TCR was induced by TCR triggering. However, in contrast to the recruitment of other TCR signaling effectors, such as the tyrosine kinase ZAP‐70 or the adaptor protein Nck (Gil et al, 2002), that is mediated by changes in the TCR itself, recruitment of β‐Arr1 to the TCR was mediated by modifying β‐Arr1. The mechanism by which TCR triggering induces the recruitment of β‐Arr1 to non‐triggered TCRs ...
BMS-777607是一种Met相关的抑制剂,作用于c-Met,Axl,Ron和Tyro3,在无细胞试验中IC50分别为3.9 nM,1.1 nM,1.8 nM和4.3 nM,作用于Met相关靶点比作用于Lck, VEGFR-2,和TrkA/B选择性高40倍,比作用于其他受体和非受体激酶选择性高500多倍。Phase 1/2。. ...
https://doi.org/10.18632/oncotarget.24859 Saurabh Agarwal, Giorgio Milazzo, Kimal Rajapakshe, Ronald Bernardi, Zaowen Chen, Eveline Barberi, Jan Koster, Giovanni Perini, Cristian Coarfa, Jason M. Shohet
LCN10兔多克隆抗体(ab108018)可与小鼠, 人样本反应并经WB实验严格验证。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
Gli insegnanti del sacro nome 1 - Introduzione 2 - Il movimento del nome sacro 3 - יהוה (Yahweh) il tetragrammaton 4 - Il nome Geova 5 - In Conclusione |div style=float: left; margin-right: 10px|
В 2003 году Pro-Logic знакомятся с DJ-ем и клубным промоутером - Руднянским Ильей ( Dj Shadow.ru ) и начинают плодотворное сотрудничество в области танцевальной культуры города. В 2003 году выходит первый сборник Волгоградских элетронных музыкантов D-Vision, параллельно Pro-Logic организуют Клубные Вторники в н-к «Жемчужина» в поддержку радио-передачи Dj Shadow-а - «Танцпол» на радио XIT-FM, где Pro-Logic, впервые в Волгограде, работают в роли клубных MC и разрывают разумы клубных мира сего под свежие мировые релизы от Dj Shadow-а. В конце 2003 года Pro-Logic выпускают программу «Клубный ХИТ» на ...
The neutrophilic granulocyte is a cytotoxic and potentially tissue-injuring cell participating in the destructive processes and symptoms seen in a variety of inflammatory diseases. Sensitive immunoassays have been introduced to measure the levels of specific secretory proteins of various inflammatory cells in blood and other body fluids. The aim has been to develop highly specific markers for each cell type. The results obtained by immunoassay have indicated that human neutrophil lipocalin (HNL) is a protein unique to the neutrophil. The present study investigated the specificity of HNL as a neutrophil marker in peripheral blood and lung tissue by using flow cytometry and immunocytochemistry. Flow cytometry and immunocytochemistry on peripheral blood showed that monoclonal antibodies to HNL only react with neutrophils and not with other types of leukocytes. Immunocytochemistry on plastic-embedded sections and on frozen sections of lung tissue showed that a cocktail of six monoclonal antibodies ...
Looking for online definition of NCK tyrosine kinase, NCKalpha in the Medical Dictionary? NCK tyrosine kinase, NCKalpha explanation free. What is NCK tyrosine kinase, NCKalpha? Meaning of NCK tyrosine kinase, NCKalpha medical term. What does NCK tyrosine kinase, NCKalpha mean?
Graded Hedgehog (Hh) signaling governs the balance of Gli transcriptional activators and repressors to specify diverse ventral cell fates in the spinal cord. It remains unclear how distinct intracellular Gli activity is generated. Here, we demonstrate that Sufu acts universally as a negative regulator of Hh signaling, whereas Kif7 inhibits Gli activity in cooperation with, and independent of, Sufu. Together, they deter naïve precursors from acquiring increasingly ventral identity. We show that Kif7 is also required to establish high intracellular Gli activity by antagonizing the Sufu-inhibition of Gli2. Strikingly, by abolishing the negative regulatory action of Sufu, diverse ventral cell fates can be specified in the absence of extracellular Hh signaling. These data suggest that Sufu is the primary regulator of graded Hh signaling and establish that the antagonistic and cooperative actions of Kif7 and Sufu are responsible for setting up distinct Gli activity in ventral cell fate specification.
JQ1 drug. Molecular model of a the experimental drug JQ1. JQ1 is a thienotriazolodiazepine, structurally related to benzodiazepines. It belongs to a class of drugs known as BET inhibitors. BET inhibitors such as JQ1 are undergoing clinical trials for treating a variety of cancers including NUT midline carcinoma. JQ1 has also been investigated for its potential in the treatment of HIV (human immunodeficiency virus) infection, as a male contraceptive, and in the treatment of heart disease. Atoms are represented as spheres and are colour-coded: carbon (grey), hydrogen (white), nitrogen (blue), oxygen (red), chlorine (green), sulphur (yellow). - Stock Image C028/8035
Abstract: A central question in Hedgehog (Hh) signaling is how evolutionarily conserved components of the pathway might use the primary cilium in mammals but not fly. We focus on Suppressor of fused (Sufu), a major Hh regulator in mammals, and reveal that Sufu controls protein levels of full-length Gli transcription factors, thus affecting the production of Gli activators and repressors essential for graded Hh responses. Surprisingly, despite ciliary localization of most Hh pathway components, regulation of Gli protein levels by Sufu is cilium-independent. We propose that Sufu-dependent processes in Hh signaling are evolutionarily conserved. Consistent with this, Sufu regulates Gli protein levels by antagonizing the activity of Spop, a conserved Gli-degrading factor. Furthermore, addition of zebrafish or fly Sufu restores Gli protein function in Sufu-deficient mammalian cells. In contrast, fly Smo is unable to translocate to the primary cilium and activate the mammalian Hh pathway. We also ...
Plasmid -962 human cyclin D1 promoter EtsB site mutant pGL3Basic from Dr. Frank McCormicks lab contains the insert CCND1 and is published in Nature. 1999 Apr 1;398(6726):422-6. This plasmid is available through Addgene.
DJ-1 is a novel oncogene and a causative gene for the familial form of Parkinsons disease (PD). DJ-1 has been shown to play roles in anti-oxidative stress by eliminating reactive oxygen species and in transcriptional regulation of genes. Loss of these functions of DJ-1 is thought to trigger the onset of PD. In this study, to identify genes for which expressions are regulated by DJ-1, DNA microarray analyses were carried out using two mouse NIH3T3 cell lines, DJ-1-knockdown cells and cells harboring an exogenously added L 166 P DJ-1 mutant found in PD patients. In both cell lines, drastic changes in expressions of genes, including genes related to stress, apoptosis, oxidative stress and neurotoxicity, were observed and changes in expressions were confirmed by RT-PCR. Of the genes identified, expression level of the extracellular superoxide dismutase (SOD 3) gene was found to decrease in DJ-1-knockdown cells, while expressions of SOD 1 and SOD 2 genes did not change. Furthermore, expression of the tau
Supplementary MaterialsAdditional file 1: Amount S1. analysis. Desk S2. Individual 15-LOX1 gene methylation level in Wager1A and NCI-H23 cells treated by PM2.5 and NNK. (DOCX 8597 kb) 13046_2019_1380_MOESM1_ESM.docx (8.3M) GUID:?E4D45034-F009-4058-81B1-2C06D29B3D25 Data Availability StatementAll relevant data are contained in the paper and its own supplementary information files. Abstract History Epidemiological observations possess showed that ambient great […]. Read More ». ...
GAS7 antibody [9H6] (growth arrest-specific 7) for FACS, WB. Anti-GAS7 mAb (GTX84464) is tested in Human samples. 100% Ab-Assurance.
マウス・ポリクローナル抗体 ab89819 交差種: Hu 適用: WB,IHC-P…Lipocalin-2 / NGAL抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody 製品。国内在庫と品質保証制度も充実。
Some tumors addiction to the over-expression of a single oncogene provides a weakness for a molecularly targeted therapy to exploit. A number of targeted
MYCN is the most commonly amplified gene in human neuroblastomas. This proto-oncogene has been overexpressed in a mouse model of the disease in order to explore the role of MYCN in this tumour. Aims: To report the histopathological features of neuroblastomas from MYCN transgenic mice. Methods: 27 neuroblastomas from hemizygous transgenic mice and 4 tumours from homozygous mice were examined histologically, and Ki67 and MYCN immunocytochemistry performed in 24 tumours. Results: Tumours obtained from MYCN transgenic mice resembled human neuroblastomas, displaying many of the features associated with stroma-poor neuroblastoma including heterogeneity of differentiation (but no overt ganglionic differentiation was seen), low levels of Schwannian stroma and a high mitosis karyorrhexis index. The tumours had a median Ki67 labelling index of 70% and all tumours expressed MYCN with a median labelling index of 68%. The most striking difference between the murine and human neuroblastomas was the presence ...
Gli proteins are the effectors of Hedgehog (Hh) signaling and have been shown to be involved in cell fate determination, proliferation and patterning in many cell types and most organs during embryo development. The Gli transcription factors activate/inhibit transcription by binding to Gli responsive genes and by interacting with the transcription complex. The Gli transcription factors have DNA binding zinc finger domains which bind to consensus sequences on their target genes to initiate or suppress transcription. Research showed that mutating the Gli zinc finger domain inhibited the proteins effect proving its role as a transcription factor. Gli proteins have an 18-amino acid region highly similar to the α-helical herpes simplex viral protein 16 activation domain.. ...
A novel oncogene related to c-mil is transduced in chicken neuroretina cells induced to proliferate by infection with an avian lymphomatosis virus.: Non-dividin
To assess evidence for the presence of a mendelian pattern of familial transmission the presence of a rare major mendelian gene for PD for a gene that influences age-dependent penetrance of WD-repeat (GRWD1) belong to WD-repeat proteins that promotes microtubule dynamics activity somewhat still carried out, this may be true as far as mendelian (nuclear) genetic mechanisms are concerned that there was no highly penetrant mendelian pattern of inheritance here they show that DJ-1 and PSF bind and regulate the major interacting-proteins with DJ-1 in dopaminergic neuronal cells which can be reversed by wild-type DJ-1 [Drosophila gain-of-function mutants identified] to regulate the expression of a neuroprotective genetic program [1.] appears to have constrained the evolution of the nonA [diss-dissonance, plus the cacophony (referred to as intron L by them, [AFX1] as are inhibited by the L-type calcium channel blockers Dmca1A (nbA-cac) are both expressed in tubules] promoter. (PSF), paraspeckle ...
Background: Neuroblastoma is a genetically heterogenic tumor diagnosed in childhood which exhibits broad clinical diversity ranging from rapid disease progression to spontaneous regression. Although amplification of the MYCN oncogene is one of the most prominent prognostic markers of this disease it is only present in around 25% of patients. Hence, additional molecular markers are needed for patients lacking MYCN amplification to enable better stratification of patient risk groups.. To date, genome wide association studies have identified few gene candidates in neuroblastoma patients that can be further developed for prognostic use in the clinic. DNA methylation is a major epigenetic mechanism for gene silencing in a wide range of human cancers and methylation sites may reveal new prognostic targets in neuroblastoma. Recent studies have suggested that the methylation status of specific gene promoters may be useful for clinically discriminating subgroups of children diagnosed with neuroblastoma. ...
In neuroblastoma, amplification of the oncogenic basic helix-loop-helix (bHLH) transcription factor (TF) MYCN is the defining prognosticator of high-risk disease, occurs in one-third of neuroblastoma, and drastically reduces overall survival rates. As a proto-oncogene, targeted MYCN overexpression in peripheral neural crest is sufficient to initiate disease in mouse models. In MYCN amplified neuroblastoma, elevated expression of the factor is crucial to maintain tumor stemness and is associated with increased proliferation and aberrant cell cycle progression, as these tumors lack the ability to arrest in G1 in response to irradiation. MYCN down-regulation broadly reverses these oncogenic phenotypes in a variety of neuroblastoma models and recent thereapeutic strategies to indirectly target MYCN production or protein stability have reduced tumor growth in vivo. These observations motivate an investigation of MYCN binding in MYCN amplified tumors as it remains fundamentally unclear how elevated levels of
Several earlier studies suggested that the E-cyclins CcnE1 and CcnE2 are functionally equivalent (10). However, more recent work also identified nonredundant functions of either CcnE1 or CcnE2 (11). HCC is associated with strong CcnE1 overexpression correlating with poor prognosis of patients, while the contribution of CcnE2 for liver cancer has barely been investigated so far (5). In a recent and elegant study, Sicinski and coworkers (12) showed that compound deletion of CcnE1 and CcnE2 prevented HCC progression in mice and halted proliferation of human HCC cells. However, this important work does not answer the question of whether CcnE1 or CcnE2 may mediate individual functions in distinct stages of hepatocarcinogenesis, which was now extensively addressed in our present study.. In our present study, ablation of CcnE1 largely prevented the development of HCC in two independent tumor models, and previous analysis indicated that inhibition of CcnE1 may also attenuate hepatocarcinogenesis in an ...