The Experts below are selected from a list of 41394 Experts worldwide ranked by ideXlab platform
E Shyam P Reddy - One of the best experts on this subject based on the ideXlab platform.
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EWS-ATF-1 Chimeric Protein in soft tissue clear cell sarcoma associates with CREB-binding Protein and interferes with p53-mediated trans-activation function
Oncogene, 2001Co-Authors: Yasuo Fujimura, Habibur Siddique, E Shyam P ReddyAbstract:The recurrent t(12;22) (q13;q12) chromosomal translocation associated with soft tissue clear cell sarcoma results in a Chimeric Protein EWS-ATF-1 that acts as a constitutive transcriptional activator. The CBP/p300 transcriptional coactivator, which links various transcriptional factors to basal transcription apparatus, participates in transcriptional activation, growth and cell cycle control and differentiation. In this study, we show that EWS-ATF-1 associates constitutively with CBP both in vitro and in vivo . Both EWS and ATF-1 fusion domains are needed for this interaction. Here, we demonstrate that EWS-ATF-1 represses p53/CBP-mediated trans -activation function. Overexpression of CBP can counteract this repressive effect of EWS-ATF-1. Taken together, these findings suggest that one of the mechanisms by which EWS-ATF-1 may cause tumors is through targeting CBP/p300 resulting in the loss of function of p53. This novel mechanism may be responsible for the development of these and other related solid tumors.
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EWS-ATF-1 Chimeric Protein in soft tissue clear cell sarcoma associates with CREB-binding Protein and interferes with p53-mediated trans-activation function
Oncogene, 2001Co-Authors: Yasuo Fujimura, Habibur Siddique, Leo Lee, Veena N Rao, E Shyam P ReddyAbstract:The recurrent t(12;22) (q13;q12) chromosomal translocation associated with soft tissue clear cell sarcoma results in a Chimeric Protein EWS-ATF-1 that acts as a constitutive transcriptional activator. The CBP/p300 transcriptional coactivator, which links various transcriptional factors to basal transcription apparatus, participates in transcriptional activation, growth and cell cycle control and differentiation. In this study, we show that EWS-ATF-1 associates constitutively with CBP both in vitro and in vivo . Both EWS and ATF-1 fusion domains are needed for this interaction. Here, we demonstrate that EWS-ATF-1 represses p53/CBP-mediated trans -activation function. Overexpression of CBP can counteract this repressive effect of EWS-ATF-1. Taken together, these findings suggest that one of the mechanisms by which EWS-ATF-1 may cause tumors is through targeting CBP/p300 resulting in the loss of function of p53. This novel mechanism may be responsible for the development of these and other related solid tumors.
Yasuo Fujimura - One of the best experts on this subject based on the ideXlab platform.
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EWS-ATF-1 Chimeric Protein in soft tissue clear cell sarcoma associates with CREB-binding Protein and interferes with p53-mediated trans-activation function
Oncogene, 2001Co-Authors: Yasuo Fujimura, Habibur Siddique, E Shyam P ReddyAbstract:The recurrent t(12;22) (q13;q12) chromosomal translocation associated with soft tissue clear cell sarcoma results in a Chimeric Protein EWS-ATF-1 that acts as a constitutive transcriptional activator. The CBP/p300 transcriptional coactivator, which links various transcriptional factors to basal transcription apparatus, participates in transcriptional activation, growth and cell cycle control and differentiation. In this study, we show that EWS-ATF-1 associates constitutively with CBP both in vitro and in vivo . Both EWS and ATF-1 fusion domains are needed for this interaction. Here, we demonstrate that EWS-ATF-1 represses p53/CBP-mediated trans -activation function. Overexpression of CBP can counteract this repressive effect of EWS-ATF-1. Taken together, these findings suggest that one of the mechanisms by which EWS-ATF-1 may cause tumors is through targeting CBP/p300 resulting in the loss of function of p53. This novel mechanism may be responsible for the development of these and other related solid tumors.
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EWS-ATF-1 Chimeric Protein in soft tissue clear cell sarcoma associates with CREB-binding Protein and interferes with p53-mediated trans-activation function
Oncogene, 2001Co-Authors: Yasuo Fujimura, Habibur Siddique, Leo Lee, Veena N Rao, E Shyam P ReddyAbstract:The recurrent t(12;22) (q13;q12) chromosomal translocation associated with soft tissue clear cell sarcoma results in a Chimeric Protein EWS-ATF-1 that acts as a constitutive transcriptional activator. The CBP/p300 transcriptional coactivator, which links various transcriptional factors to basal transcription apparatus, participates in transcriptional activation, growth and cell cycle control and differentiation. In this study, we show that EWS-ATF-1 associates constitutively with CBP both in vitro and in vivo . Both EWS and ATF-1 fusion domains are needed for this interaction. Here, we demonstrate that EWS-ATF-1 represses p53/CBP-mediated trans -activation function. Overexpression of CBP can counteract this repressive effect of EWS-ATF-1. Taken together, these findings suggest that one of the mechanisms by which EWS-ATF-1 may cause tumors is through targeting CBP/p300 resulting in the loss of function of p53. This novel mechanism may be responsible for the development of these and other related solid tumors.
Gabriel H. Travis - One of the best experts on this subject based on the ideXlab platform.
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Analysis of the rds/peripherin.rom1 complex in transgenic photoreceptors that express a Chimeric Protein.
The Journal of biological chemistry, 1999Co-Authors: Wojciech Kedzierski, Jian Weng, Gabriel H. TravisAbstract:Abstract Mice homozygous for the retinal degeneration slow (rds) mutation completely lack photoreceptor outer segments. The rds gene encodes rds/peripherin (rds), a membrane glycoProtein in the rims of rod and cone outer segment discs. rds is present as a complex with the related Protein, rom1. Here, we generated transgenic mice that express a Chimeric Protein (rom/D2) containing the intradiscal D2 loop of rds in the context of rom1. rom/D2 was N-glycosylated, formed covalent homodimers, and interacted non-covalently with itself, rds, and rom1. The rds·rom/D2 interaction was significantly more stable than the non-covalent interaction between rds and rom1 by detergent/urea titration. Analysis of mice expressing rom/D2 revealed that rds is 2.5-fold more abundant than rom1, interacts non-covalently with itself and rom1 via the D2 loop, and forms a high order complex that may extend the entire circumference of the disc. Expression of rom/D2 fully rescued the ultrastructural phenotype inrds+/− mutant mice, but it had no effect on the phenotype in rds−/− mutants. Together, these observations explain the striking differences in null phenotypes and frequencies of disease-causing mutations between the RDS andROM1 genes.
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analysis of the rds peripherin rom1 complex in transgenic photoreceptors that express a Chimeric Protein
Journal of Biological Chemistry, 1999Co-Authors: Wojciech Kedzierski, Jian Weng, Gabriel H. TravisAbstract:Abstract Mice homozygous for the retinal degeneration slow (rds) mutation completely lack photoreceptor outer segments. The rds gene encodes rds/peripherin (rds), a membrane glycoProtein in the rims of rod and cone outer segment discs. rds is present as a complex with the related Protein, rom1. Here, we generated transgenic mice that express a Chimeric Protein (rom/D2) containing the intradiscal D2 loop of rds in the context of rom1. rom/D2 was N-glycosylated, formed covalent homodimers, and interacted non-covalently with itself, rds, and rom1. The rds·rom/D2 interaction was significantly more stable than the non-covalent interaction between rds and rom1 by detergent/urea titration. Analysis of mice expressing rom/D2 revealed that rds is 2.5-fold more abundant than rom1, interacts non-covalently with itself and rom1 via the D2 loop, and forms a high order complex that may extend the entire circumference of the disc. Expression of rom/D2 fully rescued the ultrastructural phenotype inrds+/− mutant mice, but it had no effect on the phenotype in rds−/− mutants. Together, these observations explain the striking differences in null phenotypes and frequencies of disease-causing mutations between the RDS andROM1 genes.
Bruce Beutler - One of the best experts on this subject based on the ideXlab platform.
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a tumor necrosis factor tnf receptor igg heavy chain Chimeric Protein as a bivalent antagonist of tnf activity
Journal of Experimental Medicine, 1991Co-Authors: Karsten Peppel, David Crawford, Bruce BeutlerAbstract:Using a multistep polymerase chain reaction method, we have produced a construct in which a cDNA sequence encoding the extracellular domain of the human 55-kD tumor necrosis factor (TNF) receptor is attached to a sequence encoding the Fc portion and hinge region of a mouse IgG1 heavy chain through an oligomer encoding a thrombin-sensitive peptide linker. This construct was placed downstream from a cytomegalovirus promoter sequence, and expressed in Chinese hamster ovary cells. A secreted Protein, capable of binding TNF and inactivating it, was produced by the transfected cells. Molecular characterization revealed that this soluble version of the TNF receptor was dimeric. Moreover, the Protein could be quantitatively cleaved by treatment with thrombin. However, the monovalent extracellular domain prepared in this way has a greatly reduced TNF inhibitory activity compared with that of the bivalent inhibitor. Perhaps because of its high affinity for TNF, the Chimeric Protein is far more effective as a TNF inhibitor than are neutralizing monoclonal antibodies. This molecule may prove very useful as a reagent for the antagonism and assay of TNF and lymphotoxin from diverse species in health and disease, and as a means of deciphering the exact mechanism through which TNF interacts with the 55-kD receptor.
Habibur Siddique - One of the best experts on this subject based on the ideXlab platform.
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EWS-ATF-1 Chimeric Protein in soft tissue clear cell sarcoma associates with CREB-binding Protein and interferes with p53-mediated trans-activation function
Oncogene, 2001Co-Authors: Yasuo Fujimura, Habibur Siddique, E Shyam P ReddyAbstract:The recurrent t(12;22) (q13;q12) chromosomal translocation associated with soft tissue clear cell sarcoma results in a Chimeric Protein EWS-ATF-1 that acts as a constitutive transcriptional activator. The CBP/p300 transcriptional coactivator, which links various transcriptional factors to basal transcription apparatus, participates in transcriptional activation, growth and cell cycle control and differentiation. In this study, we show that EWS-ATF-1 associates constitutively with CBP both in vitro and in vivo . Both EWS and ATF-1 fusion domains are needed for this interaction. Here, we demonstrate that EWS-ATF-1 represses p53/CBP-mediated trans -activation function. Overexpression of CBP can counteract this repressive effect of EWS-ATF-1. Taken together, these findings suggest that one of the mechanisms by which EWS-ATF-1 may cause tumors is through targeting CBP/p300 resulting in the loss of function of p53. This novel mechanism may be responsible for the development of these and other related solid tumors.
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EWS-ATF-1 Chimeric Protein in soft tissue clear cell sarcoma associates with CREB-binding Protein and interferes with p53-mediated trans-activation function
Oncogene, 2001Co-Authors: Yasuo Fujimura, Habibur Siddique, Leo Lee, Veena N Rao, E Shyam P ReddyAbstract:The recurrent t(12;22) (q13;q12) chromosomal translocation associated with soft tissue clear cell sarcoma results in a Chimeric Protein EWS-ATF-1 that acts as a constitutive transcriptional activator. The CBP/p300 transcriptional coactivator, which links various transcriptional factors to basal transcription apparatus, participates in transcriptional activation, growth and cell cycle control and differentiation. In this study, we show that EWS-ATF-1 associates constitutively with CBP both in vitro and in vivo . Both EWS and ATF-1 fusion domains are needed for this interaction. Here, we demonstrate that EWS-ATF-1 represses p53/CBP-mediated trans -activation function. Overexpression of CBP can counteract this repressive effect of EWS-ATF-1. Taken together, these findings suggest that one of the mechanisms by which EWS-ATF-1 may cause tumors is through targeting CBP/p300 resulting in the loss of function of p53. This novel mechanism may be responsible for the development of these and other related solid tumors.