Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using a synthetic peptide that encompasses the zinc finger domain of the eukaryotic transcription factor Sp1, we produced a number of monoclonal antibodies that specifically reacted with the target antigen. Analysis by competitive inhibition assay of five of the monoclonal antibodies revealed that they all recognized a dominant epitope in the synthetic peptide and reacted strongly to recombinantly synthesized beta-galactosidase-Sp1 fusion polypeptide. To determine cellular distribution of Sp1-like molecules, cytoplasmic and nuclear proteins from human lung fibroblasts (HFL-1) and a human rhabdomyosarcoma cell line (A204) were immunoblotted and reacted with our antibodies. In addition to the well characterized 95 Kd and 105 Kd proteins, considered to be the authentic Sp1 polypeptide, a number of other cellular proteins reacted with these antibodies. Immunofluorescence staining of the cells with mAb to the zinc finger of Sp1 also revealed cell-specific differences in intracellular distribution of Sp1-like molecules. Both cytoplasmic and nuclear staining was readily observed in the rhabdomyosarcoma cells. In contrast, while some HFL-1 cells exhibited staining of only cytoplasm, both cytoplasmic and nuclear immunofluorescence was seen in others.
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PMID:Generation of monoclonal antibodies to the zinc finger domain of the eukaryotic transcription factor Sp1. 201 Nov 20

ZT3, isolated from a murine muscle cell cDNA library by a low-stringency hybridization, encodes a zinc finger domain containing factor with a transcript of 5.0 kb. A 3' 2.5 kb partial nucleotide sequence contains an ORF of 1.5 kb where 17 canonical C2H2 zinc finger domains organized in tandem were identified. It maps on mouse chromosome 11, close to two mutations which affect skeletal formation. ZT3 expression depends upon differentiation of myogenic cells in culture, since it is upregulated with myogenin and inhibited in scr-transfected C2C12 cells. ZT3 is not expressed in NIH3T3 or C3H10T1/2 fibroblasts, but is induced when fibroblasts are myogenically converted by transfection with the muscle regulatory genes (MRFs). Its expression is also upregulated in the rhabdomyosarcoma cell line RD induced to myogenic differentiation by TPA treatment. In postimplantation embryos, ZT3 is diffusely expressed but higher expression is detectable in the neural tube and encephalic vesicles, in the somites and, at a high level, in the limb buds as they form. During further development ZT3 is expressed in many tissues of neuroectodermal and mesodermal origin, but its expression decreases during fetal development and in the adult it is restricted to skeletal and cardiac muscle and to spleen. This pattern of expression suggests a possible role played by ZT3 in differentiating skeletal muscle. Its expression in other tissues is compatible with the suggestion that members of this class of DNA-binding factors play different roles during post-implantation development and in the adult life.
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PMID:Differentiation dependent expression in muscle cells of ZT3, a novel zinc finger factor differentially expressed in embryonic and adult tissues. 880 10

The utrophin gene codes for a large cytoskeletal protein closely related to dystrophin which, in the absence of dystrophin, can functionally substitute it. Utrophin is transcribed by two independently regulated promoters about 50 kb apart. The upstream promoter is TATA-less and contains a functional GABP binding site which, in muscle, restricts the promoter activity to post-synaptic nuclei. Transient transfections analysis of mutant promoters in rhabdomyosarcoma cells showed that the upstream promoter contains three functional GC elements that are recognised by Sp1 and Sp3 factors in vitro. Co-transfections of the promoter with Sp1, Sp3 and GABP factors in Drosophila SL2 Schneider cells, which lack of endogenous Sp factors, demonstrated that both Sp1 and Sp3 are positive regulators of the utrophin promoter and that they activate transcription synergistically with GABP. Consistent with this result, we observed physical interaction of both Sp factors with the GABPalpha subunit in vitro. Functional domain interaction analysis of Sp1 and Sp3 revealed that both factors interact with GABPalpha through their DNA binding zinc finger domain. The modulation and correct interaction between Sp1, Sp3 and GABP in muscle cells may be critical for the regulation of the utrophin promoter, and provide new targets for therapies of Duchenne muscular dystrophy.
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PMID:Sp1 and Sp3 physically interact and co-operate with GABP for the activation of the utrophin promoter. 1123 13

The Hedgehog-regulated transcription factors GLI1 and GLI2 play overlapping roles in development and disease; however, the mechanisms underlying their interplay remain elusive. We report for the first time that GLI1 and GLI2 physically and functionally interact in cancer cells. GLI1 and GLI2 were shown to co-immunoprecipitate in PANC1 pancreatic cancer cells and RMS13 rhabdomyosarcoma cells. Mapping analysis demonstrated that the zinc finger domains of both proteins are required for their heteromerization. RNAi knockdown of either GLI1 or GLI2 inhibited expression of many well-characterized GLI target genes (BCL2, MYCN, PTCH2, IL7 and CCND1) in PANC1 cells, whereas PTCH1 expression was only inhibited by GLI1 depletion. qPCR screening of a large set of putative canonical and non-canonical Hedgehog/GLI targets identified further genes (e.g. E2F1, BMP1, CDK2) strongly down-regulated by GLI1 and/or GLI2 depletion in PANC1 cells, and demonstrated that ANO1, AQP1 and SOCS1 are up-regulated by knockdown of either GLI1 or GLI2. Chromatin immunoprecipitation showed that GLI1 and GLI2 occupied the same regions at the BCL2, MYCN and CCND1 promoters. Furthermore, depletion of GLI1 inhibited GLI2 occupancy at these promoters, suggesting that GLI1/GLI2 interaction is required for the recruitment of GLI2 to these sites. Together, these findings indicate that GLI1 and GLI2 co-ordinately regulate the transcription of some genes, and provide mechanistic insight into the roles of GLI proteins in carcinogenesis.
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PMID:GLI1/GLI2 functional interplay is required to control Hedgehog/GLI targets gene expression. 3276 32