The Experts below are selected from a list of 3465 Experts worldwide ranked by ideXlab platform
Akira Kudo - One of the best experts on this subject based on the ideXlab platform.
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<B>PreB> B Lymphocyte specific transcriptional control of the mouse v<B>PreB>B gene
European Journal of Immunology, 1992Co-Authors: Taijiro Okabe, Steven R. Bauer, Akira KudoAbstract:The V<B>PreB>B genes, which encode surrogate immunogloBulin light chain molecules, are ex<B>PreB>ssed as RNA almost exclusively in <B>PreB>-B cells. We have investigated the transcriptional control mechanisms which are responsiBle for the <B>PreB>-B cell-specific RNA ex<B>PreB>ssion of the mouse V<B>PreB>B1 and V<B>PreB>B2 genes. Nuclear run-on analyses demonstrate that the <B>PreB>-B cell-specific ex<B>PreB>ssion of Both V<B>PreB>B genes is controlled primarily at the level of initiation of transcription. S1 nuclease protection-mapping defined two or three major start sites of transcription for the V<B>PreB>B genes. To find a promoter and other potential cis-acting regulatory elements, a 700-Bp fragment 5' of the transcription start sites of the V<B>PreB>B1 gene was used in gene transfer experiments and found to act as a promoter in <B>PreB>-B Lymphocytes. Deletion experiments showed that 191 Bp upstream of the most 5' transcription start site is required for the <B>PreB>-B cell promoter activity. DNA sequence analysis of the 5' region of the mouse V<B>PreB>B1, V<B>PreB>B2 and human V<B>PreB>B genes reveal that this region of approximately 200 Bp is strongly conserved. This 200-Bp promoter region contains several conserved nucleotide sequence motifs which may act to mediate the <B>PreB>-B cell-specific transcription of the V<B>PreB>B genes.
John J Oshea - One of the best experts on this subject based on the ideXlab platform.
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ewing sarcoma gene ews is essential for meiosis and B Lymphocyte development
Journal of Clinical Investigation, 2007Co-Authors: Hongjie Li, Alissa Parmelee, Mark A Bryant, Chu-xia Deng, Wendy T. Watford, Cuiling Li, John J OsheaAbstract:: Ewing sarcoma gene EWS encodes a putative RNA-Binding protein with proposed roles in transcription and splicing, But its physiological role in vivo remains undefined. Here, we have generated Ews-deficient mice and demonstrated that EWS is required for the completion of B cell development and meiosis. Analysis of Ews(-/-) Lymphocytes revealed a cell-autonomous defect in <B>PreB>cursor B Lymphocyte (<B>PreB>-B Lymphocyte) development. During meiosis, Ews-null spermatocytes were deficient in XY Bivalent formation and showed reduced meiotic recomBination, resulting in massive apoptosis and complete arrest in gamete maturation. Inactivation of Ews in mouse emBryonic fiBroBlasts resulted in <B>PreB>mature cellular senescence, and the mutant animals showed hypersensitivity to ionizing radiation. Finally, we showed that EWS interacts with lamin A/C and that loss of EWS results in a reduced lamin A/C ex<B>PreB>ssion. Our findings reveal essential functions for EWS in <B>PreB>-B cell development and meiosis, with proposed roles in DNA pairing and recomBination/repair mechanisms. Furthermore, we demonstrate a novel role of EWS in cellular senescence, possiBly through its interaction and modulation of lamin A/C.
Michael Lee - One of the best experts on this subject based on the ideXlab platform.
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raf independent and mekk1 dependent activation of nf κB By hydrogen peroxide in 70z 3 <B>PreB> B Lymphocyte tumor cells
Journal of Cellular Biochemistry, 2003Co-Authors: Michael Lee, Woo Suk KohAbstract:We have <B>PreB>viously demonstrated that hydrogen peroxide (H(2)O(2)) treatment of murine 70Z/3 <B>PreB>-B Lymphocytes inhiBits the immune response to lipopolysaccharide By attenuating signaling through c-Jun N-terminal kinase (JNK) activation. In the <B>PreB>sent study, we further examined the signaling intermediates responsiBle for immunosup<B>PreB>ssion By H(2)O(2), focusing on NF-kappaB, a dimeric transcription factor whose activation is implicated in a numBer of immune response. Treatment of 70Z/3 <B>PreB>-B cells with H(2)O(2) caused activation of NF-kappaB in the nuclei By detection of NF-kappaB specific DNA Binding, concomitant with phosphorylation of IkappaBalpha. H(2)O(2) stimulation of NF-kappaB occurred within 20 min of treatment, reached maximum level at 60 min, and sustained for 2 h or more. Especially, MEK1 may contriBute to H(2)O(2)-induced NF-kappaB activation as shown in the inhiBition of NF-kappaB Binding activity By the MEK1 inhiBitor, PD 98059, and H(2)O(2)-induced MEK1 activation. However, H(2)O(2) exhiBited no effect on the activity of Raf-1 kinase, which was an upstream activator of MEK1. Furthermore, B-58l and alpha-hydroxyfarnesylphosphonic acid, two inhiBitors of Ras, did not Block NF-kappaB activation. In addition, the transient transfection of a dominant negative Ras (RasN17) construct showed a negligiBle inhiBitory effect on the activation of NF-kappaB By H(2)O(2). Instead, treatment of 70Z/3 cells with H(2)O(2) resulted in the activation of MAPK kinase kinase 1 (MEKK1) as well as JNK. Therefore, our data suggest that H(2)O(2) regulates the activity of NF-kappaB By MEK1 activation through MEKK1-dependent But Ras/Raf-independent mechanism.
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paclitaxel induced immune sup<B>PreB>ssion is associated with nf κB activation via conventional pkc isotypes in lipopolysaccharide stimulated 70z 3 <B>PreB> B Lymphocyte tumor cells
Molecular Pharmacology, 2001Co-Authors: Michael Lee, Young Jin JeonAbstract:Paclitaxel, a potent antitumor agent, has Been shown to Be lipopolysaccharide (LPS) mimetic in mice, stimulating signaling pathways and gene ex<B>PreB>ssion indistinguishaBly from LPS. In the <B>PreB>sent study, we showed the intracellular signaling pathway of paclitaxel-induced nuclear factor-κB (NF-κB) activation and its sup<B>PreB>ssive effect on LPS-induced signaling in murine 70Z/3 <B>PreB>-B cells. Stimulation of 70Z/3 cells with LPS for 30 min caused activation of NF-κB in the nuclei By detection of DNA-protein Binding specific to NF-κB. Similarly, paclitaxel also produced a marked and dose-related NF-κB activation. However, <B>PreB>treatment of cells with 10 μM paclitaxel for 18 h resulted in complete inhiBition of LPS-mediated NF-κB activation. Interestingly, the activity of IκB kinase (IKK-β), which plays an essential role in NF-κB activation through IκB phosphorylation, was largely enhanced in paclitaxel-treated cells, detected as IκBα phosphorylation. Because protein kinase C (PKC) is implicated in the activation of NF-κB via IKK-β, the effect of paclitaxel on PKC activation was also measured. It was shown that NF-κB nuclear translocation and DNA Binding in response to paclitaxel was completely Blocked By the conventional PKC inhiBitor, Go 6976. Moreover, immunoBlotting analysis with paclitaxel-treated cell extract demonstrated that the conventional PKC isotype PKC-α was found to Be involved in the regulation of paclitaxel-induced NF-κB activation, as determined By electrophoretic moBility shift of PKC. Therefore, these data suggest that paclitaxel may activate IKK-β via conventional PKC isotypes, resulting in NF-κB activation and, finally, desensitization of LPS-induciBle signaling pathway in 70Z/3 <B>PreB>-B cells.
Taijiro Okabe - One of the best experts on this subject based on the ideXlab platform.
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<B>PreB> B Lymphocyte specific transcriptional control of the mouse v<B>PreB>B gene
European Journal of Immunology, 1992Co-Authors: Taijiro Okabe, Steven R. Bauer, Akira KudoAbstract:The V<B>PreB>B genes, which encode surrogate immunogloBulin light chain molecules, are ex<B>PreB>ssed as RNA almost exclusively in <B>PreB>-B cells. We have investigated the transcriptional control mechanisms which are responsiBle for the <B>PreB>-B cell-specific RNA ex<B>PreB>ssion of the mouse V<B>PreB>B1 and V<B>PreB>B2 genes. Nuclear run-on analyses demonstrate that the <B>PreB>-B cell-specific ex<B>PreB>ssion of Both V<B>PreB>B genes is controlled primarily at the level of initiation of transcription. S1 nuclease protection-mapping defined two or three major start sites of transcription for the V<B>PreB>B genes. To find a promoter and other potential cis-acting regulatory elements, a 700-Bp fragment 5' of the transcription start sites of the V<B>PreB>B1 gene was used in gene transfer experiments and found to act as a promoter in <B>PreB>-B Lymphocytes. Deletion experiments showed that 191 Bp upstream of the most 5' transcription start site is required for the <B>PreB>-B cell promoter activity. DNA sequence analysis of the 5' region of the mouse V<B>PreB>B1, V<B>PreB>B2 and human V<B>PreB>B genes reveal that this region of approximately 200 Bp is strongly conserved. This 200-Bp promoter region contains several conserved nucleotide sequence motifs which may act to mediate the <B>PreB>-B cell-specific transcription of the V<B>PreB>B genes.
Randolph Wall - One of the best experts on this subject based on the ideXlab platform.
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lipopolysaccharide induced nf kappa B activation in mouse 70z 3 <B>PreB> B Lymphocytes is inhiBited By mevinolin and 5 methylthioadenosine roles of protein iso<B>PreB>nylation and carBoxyl methylation reactions
Molecular and Cellular Biology, 1992Co-Authors: Ronald E Law, J B Stimmel, M Damore, C Carter, Steven Clarke, Randolph WallAbstract:We show that Both the lipopolysaccharide (LPS)-induced activation of NF-kappa DNA Binding and kappa gene ex<B>PreB>ssion are Blocked By treating murine <B>PreB>-B Lymphocyte 70Z/3 cells with 5'-methylthioadenosine (MTA), an inhiBitor of several S-adenosylmethionine-dependent methylation reactions. We further show that the LPS-induced incorporation of radioactivity from [methyl-3H]methionine into methyl ester-like linkages on a group of memBrane polypeptides is also inhiBited By MTA treatment, suggesting the involvement of protein methylation reactions in the LPS signal transduction pathway. We also find that NF-kappa B and kappa gene activation in LPS-treated 70Z/3 cells is Blocked By mevinolin, an inhiBitor that <B>PreB>vents protein iso<B>PreB>nylation. Interestingly, mevinolin-treated cells also exhiBited a marked reduction in the methylation of memBrane proteins. Neither MTA nor mevinolin significantly inhiBited NF-kappa B activation By phorBol myristate acetate, suggesting that these agents act early in signal transduction. These results provide the first evidence that carBoxyl methylated and/or iso<B>PreB>nylated proteins play an essential role in the LPS-signaling pathway.