Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Production of recombinant proteins that are not secreted outside the producing cells usually requires purification steps that can result in significant yield reductions and loss of biological activity. Using insect cells as a model system to devise the means for secreting recombinant proteins that are not normally destined for secretion outside the producing cells, we initially examined the ability of an insect-specific signal peptide sequence to direct secretion of two intracellular proteins (the cytoplasmic enzyme chloramphenicol acetyl transferase [CAT] and the nuclear protein Bombyx mori chorion factor 1 [BmCF1]) expressed in transfected silkmoth cells. Although this signal sequence functioned efficiently as a chimera with normally secreted proteins, it failed to secrete CAT and BmCF1, suggesting that additional signals are required for passage of these polypeptides through the secretion pathway. For this reason, we also generated a secretion module consisting of the secreted protein juvenile hormone esterase (JHE), a spacer region containing a histidine tag and an endopeptidase cleavage site, to which coding sequences of choice can be cloned as C-terminal extensions. In C-terminal fusions with the CAT and BmCF1 open reading frames, the N-terminal JHE moiety was able to provide all the signals necessary for secretion of CAT and BmCF1 into the extracellular environment. The histidine tag present in the spacer region allowed purification of fusion proteins by metal affinity chromatography under nondenaturing conditions, and the enteropeptidase cleavage site was recognized and cleaved by the cognate protease causing the release of the intracellular proteins from the secretion module. We also show that another secreted protein, human granulocyte-macrophage colony stimulating factor (GM-CSF) can substitute for JHE in the secretion module and that these secretion modules can function in mammalian cells.
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PMID:Secretion of cytoplasmic and nuclear proteins from animal cells using novel secretion modules. 1094 1

We showed that the LAF4 gene on 2q11.2-12 was fused to the MLL gene on 11q23 in a pediatric patient with CD10 positive acute lymphoblastic leukemia (ALL) having t(2;11)(q11;q23). The LAF4 gene, which encodes a lymphoid nuclear protein of 1227 amino acids with transactivation potential, is thought to have a role in early lymphoid development. The LAF4 protein was homologous to AF4 and AF5q31 proteins that are fused to MLL in infant early pre-B ALL and the breakpoint of LAF4 was located within the region homologous to the transactivation domain of AF4 and AF5q31. Expression of the 8.5-kb LAF4 transcript was detected in the adult heart, brain, and placenta and in the fetal brain. LAF4 expression was found to be higher in ALL cell lines than in AML and Epstein-Barr virus-transformed B-lymphocyte cell lines. These findings suggest that LAF4, AF4 and AF5q31 might define a new family particularly involved in the pathogenesis of 11q23-associated ALL.
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PMID:Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23). 1274 8

The identification of an outer layer of myoepithelial cells is a valuable clue in the differential diagnosis of breast lesions. Myoepithelial cells can usually be appreciated with standard hematoxylin-eosin stains, however in pathology practice one encounters difficult cases, particularly in core biopsy specimens. There are several reported markers for the immunohistochemical detection of myoepithelial cells. Smooth muscle specific proteins, such as smooth muscle actin, smooth muscle myosin heavy chain, calponin and h-caldesmone are utilized to highlight myoepithelium. Smooth muscle actin is the most commonly used and has been established as a specific and sensitive marker. However, sometimes the staining can not be interpreted, since actin stains stromal fibroblasts and vascular smooth muscle cells as well. S100 protein and specific cytokeratins (keratins 5,7,14 and 17) also stain myoepithelial cells, but the staining is not specific and is not optimally sensitive. Maspin and CD10 are relatively new and promising markers. The nuclear protein p63 has attracted much attention in recent reports. p63-positive myoepithelial cells have been shown to surround benign epithelial lesions and form a consistent, although discontinuous, rim around epithelial cells in carcinomas in situ. No staining has been noted in infiltrative carcinomas. p63-immunostaining is nuclear and so it is easily appreciated, even in cytologic preparations. It is also highly specific since neither stromal fibroblasts nor vascular smooth muscle cells are stained. In conclusion, it appears that p63 is a sensitive and specific myoepithelial marker and may be included in immunohistochemical panels aiming at identifying myoepithelial cells in problematic breast lesions.
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PMID:The usefulness of p63 as a marker of breast myoepithelial cells. 1475 23

The PHEX gene encodes an endopeptidase expressed in osteoblasts that inactivates an uncharacterized peptide hormone, phosphatonin, which suppresses bone mineralization as well as renal phosphate reabsorption and vitamin D bioactivation. We demonstrate that 1alpha-25-dihydroxyvitamin D (1,25(OH)2D3), the, active renal vitamin D metabolite, decreases PHEX mRNA in the rat osteoblastic cell line, UMR-106, as well as in mouse calvaria. Promoter/reporter construct analysis of the murine PHEX gene in transfected UMR-106 cells localized the repressive effect of 1,25(OH)2D3 to the -133 to -74 bp region, and gel mobility shift experiments revealed that 1,25(OH)2D3 treatment of the cells diminished the binding of a nuclear protein(s) to a stretch of 17 adenines from bp -116 to -100 in the proximal PHEX promoter. Either overexpression of a dominant-negative vitamin D receptor (VDR) or deletion of this sequence of 17 A-T base pairs abolished the repressive effect of 1,25(OH)2D3 by attenuating basal promoter activity, indicating that this region mediates the 1,25(OH)2D3 response and is involved in basal transcription. South-western blot analysis and DNA affinity purification show that an unidentified 110 kDa nuclear protein binds to the poly(A) element. Because 1,25(OH)2D3-liganded VDR neither binds to the polyadenine region of the PHEX promoter nor directly influences the association of the 110 kDa transfactor, we conclude that 1,25(OH)2D3 indirectly decreases PHEX expression via VDR-mediated repression (or modification) of this novel transactivator. Thus, we have identified a cis-element required for PHEX gene transcription that participates in negative feedback control of PHEX expression and thereby modulates the actions of phosphatonin.
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PMID:1,25-dihydroxyvitamin D3 down-regulation of PHEX gene expression is mediated by apparent repression of a 110 kDa transfactor that binds to a polyadenine element in the promoter. 1533 62

The immunohistochemical detection of myoepithelial cells in benign sclerosing lesions of the breast is useful in distinguishing them from tubular carcinoma. So far, this detection has been carried out using antibodies against cytoskeletal proteins, such as alpha-smooth muscle actin (1A4) and calponin. However, the specificity of these markers has been questioned since they may be expressed in stromal myofibroblasts and vascular smooth muscle. Recently, two novel myoepithelial markers have been described: the nuclear protein p63, a member of the p53 family, and the surface antigen CD10, also known as common acute lymphoblastic leukemia antigen (CALLA). The authors assessed the use of p63 and CD10 in the differential diagnosis between benign sclerosing lesions, such as sclerosing adenosis and radial scar, and tubular carcinoma, in comparison to the traditional myoepithelial markers 1A4 and calponin. p63, CD10, 1A4, and calponin were expressed in myoepithelial cells of all benign lesions and were consistently negative in all cases of tubular carcinoma. In contrast to cytoskeletal proteins, p63 and CD10 were mostly confined to myoepithelial cells and thus were more specific than the traditional counterparts. However, 1A4 was more intensely expressed and more reproducible than the novel markers. In conclusion, p63 and CD10 may be used as a complement to 1A4 in distinguishing benign sclerosing lesions from tubular carcinoma of the breast.
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PMID:p63 and CD10: reliable markers in discriminating benign sclerosing lesions from tubular carcinoma of the breast? 1654 Jul 34