Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four variant AE1 anion exchangers with predicted molecular masses of approximately 99, approximately 102, approximately 104, and approximately 108 kDa are expressed in chicken erythroid cells. These variant polypeptides differ in sequence only at the N terminus of their cytoplasmic domains. Molecular analyses have shown that transcripts derived from both of the erythroid-specific promoters, P1 and P2, encode all four of these AE1 anion exchanger variants. However, quantitative RNase protection analyses have shown that the transcripts derived from the P1 promoter are much more prevalent than those derived from the P2 promoter. Reverse transcriptase polymerase chain reaction studies have indicated that the extensive diversity in the transcripts derived from the AE1 gene occurs both in primitive and definitive lineage erythroid cells. Transient transfection analyses using human erythroleukemia cells have investigated the functional significance of the alternative sequences at the N terminus of these variant exchangers. These studies have shown that the erythroid AE1 variants are sorted to different membrane compartments in these cells. The approximately 99- and approximately 102-kDa variants are primarily sorted to the plasma membrane, whereas the approximately 108-kDa variant is retained in a perinuclear compartment. These results suggest that the alternative N-terminal cytoplasmic sequences of these polypeptides may serve as signals to direct these variant transporters to different membrane compartments within cells.
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PMID:Four variant chicken erythroid AE1 anion exchangers. Role of the alternative N-terminal sequences in intracellular targeting in transfected human erythroleukemia cells. 764 85

The anion transporter, band 3, is a ubiquitous protein. It is present in brain and all other tissues examined. Not only is band 3 present in cell membranes, but also in nuclear, Golgi and mitochondria membranes. There are four isoforms of band 3, the anion exchanger (AE) proteins, thus far discovered. They are products of different genes. Lymphocytes are reported to contain AE2, but not AE1. We hypothesized that induction or up-regulation of AE1 occurs when lymphocytes are transformed as an initial event in the path to malignancy. We transformed lymphocytes containing a single base mutation with Epstein Barr Virus (EBV). The mutation of band 3, high transport band 3 (HTbd3), exhibits anion transport that is 2-3 times normal in erythrocytes which contain AE1. This facilitated our identification of AE1 since the probability that 2 different gene products would have the same mutation approaches zero. Thus, we have a base mutation in addition to linear sequence to identify AE1. A 133 base pair (bp) fragment including the affected region was amplified from the mRNA of lymphocytes from the HTbd3 mutant. AE1 primers were used to amplify regions of interest. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to generate cDNA which was sequenced. The sequence of the crucial 133 base pair segment from high transport lymphocytes was 100% identical to the sequence published for the red blood cell band 3 of the same mutant. As reported previously for erythrocytes, this mutation is a C-->T base change which changes a proline to leucine in the protein sequence. Restriction enzyme digests of AE1 cDNA from normal and HTBD3 lymphocytes confirmed that the proposita was homozygous for the mutation, and showed the father to be heterozygous. Anion transport was increased in HTbd3 EBV transformed lymphocytes, as was the case with HTbd3 erythrocytes. AE2 was identified in lymphocytes by sequence. Thus, EBV transformed lymphocytes express the erythroid band 3 (AE1) in addition to AE2.
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PMID:Human erythroid band 3 "anion exchanger 1" is expressed in transformed lymphocytes. 896 Jul 72

Desmoplastic small round cell tumor (DSRCT) is a unique, highly aggressive neoplasm that chiefly affects male adolescents and young adults. This tumor is characterized by nests of small undifferentiated cells that show immunohistochemical evidence of epithelial, mesenchymal, and neural differentiation. We report two cases of DSRCT that lacked immunohistochemical evidence of epithelial differentiation, but were found to have the fusion transcripts characteristic of this tumor. Both patients (a 41-year-old male and a 31-year-old female) presented with large intra-abdominal masses. After diagnostic biopsy, both were treated with multi-agent chemotherapy. One patient expired 18 days after diagnosis, and the other is currently alive 28 months later. Histologically, both tumors had the characteristic features of DSRCT and were composed of small round cells with hyperchromatic nuclei and scanty cytoplasm. In one of the cases, perinuclear intracytoplasmic hyaline inclusions were seen. Immunohistochemically, neither case expressed any of the epithelial markers tested, including AE1/AE3, CAM 5.2 and EMA. Both tumors were diffusely immunoreactive for desmin with a prominent globoid "dot-like" pattern of staining in one case. Both tumors stained for vimentin, neuron specific enolase, and synaptophysin, but were negative for CD99, muscle-specific actin, and myogenin. Reverse transcriptase-polymerase chain reaction revealed EWS-WT1 fusion transcripts characteristic of this neoplasm. In conclusion, we describe two cases of DSRCT that lacked immunohistochemical evidence of epithelial differentiation but had histologic and other immunohistochemical features which suggested this diagnosis. The ability to confirm the diagnosis of this rare tumor using molecular genetic techniques is particularly useful in those cases with unusual histologic or immunophenotypic features.
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PMID:Cytokeratin-negative desmoplastic small round cell tumor: a report of two cases emphasizing the utility of reverse transcriptase-polymerase chain reaction. 1049 92

Medical therapy of glaucoma commonly aims at slowing aqueous humor formation by the ocular ciliary epithelial bilayer, but underlying mechanisms are poorly understood. The first step in secretion is NaCl uptake from the stroma into the pigmented ciliary epithelial (PE) cell layer by electroneutral transporters. After crossing gap junctions into the nonpigmented ciliary epithelial (NPE) cell layer, solute is released into the aqueous humor. Published data have indicated that both paired Na+/H+ and Cl-/HCO3- antiporters and the Na+-K+-2Cl- symporter are involved in net uptake. The molecular identities of the paired antiporters have not been elucidated. We have studied continuously cultured bovine PE cells. Acid-activated 22Na+ uptake was inhibited by cariporide, EIPA (ethyl-isopropyl-amiloride) and amiloride, at concentrations characteristic of the NHE-1 isoform. Videomicroscopy of BCECF-loaded PE cells verified the presence of an EIPA-inhibitable Na+/H+ antiporter. Removing external Cl- also triggered an alkalinization, which was Na+-independent and could be inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Application of hypotonicity followed by return to isotonicity triggered a regulatory volume increase, which was pharmacologically similar to the uptake mechanisms described for intact rabbit ciliary epithelium. Reverse transcriptase polymerase chain reaction (RT-PCR) amplification of RNA from the human ciliary body detected expression of the AE2 Cl-/HCO3- exchanger, but not of AE1, cAE3 or bAE3. Immunostaining of bovine PE cells also revealed the presence of AE2 epitope. We conclude that paired NHE-1 Na+/H+ and AE2 Cl-/HCO3- antiporters are important components in the initial step in aqueous humor formation.
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PMID:Na+/H+ and CI-/HCO3-antiporters of bovine pigmented ciliary epithelial cells. 1100 5

Anion exchangers (AE) are transmembrane proteins catalyzing electroneutral exchange of Cl(-) for HCO3-. To date, three different genes coding for this protein, AE1, AE2 and AE3, have been identified in many species. AE1 is considered to be the unique anion exchanger expressed in erythrocytes. In this paper we propose the presence of three different AEs in skate erythrocytes, a skAE1, a skAE2 and a skAE3, cloned by RT-PCR (reverse-transcriptase polymerase chain reaction). These three skAE have a similar predicted secondary structure. All three skAE are divided in two main domains: a hydrophilic cytoplasmic N-terminal domain and a C-terminal domain crossing the lipid bilayer at least 12 times. The greatest similarity is found in the membrane-spanning domain of the three skAE. The size as well as the amino-acid sequence of the cytoplasmic domain differ significantly among three anion exchangers. Functional expression studies in Xenopus oocytes led to the conclusion that skAE-1 and -2 share some functional features (Cl-dependence and DIDS sensitivity). The skAE3 could not be expressed in Xenopus oocytes. These data are in agreement with expression data obtained with AEs of different species utilizing the oocyte system. It is highly probable that these three new AE sequences come from three different genes, thus suggesting for the first time the presence of the three AE genes in Chondrichthyes.
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PMID:Evidence for the presence of three different anion exchangers in a red cell. Functional expression studies in Xenopus oocytes. 1287 59

This paper discusses the diversity of synovial sarcomas (SSs) [biphasic (BSS), monophasic fibrous (MFSS), and poorly differentiated (PDSS)] and tissue microarray (TMA) evaluation of the immunophenotypic and histological progression of SSs in nude mice using three TMAs comprising 11 primary SSs (8 MFSSs, 2 BSSs, and 1 PDSS) and their xenografts. BSS and MFSS progressively transformed to a similar undifferentiated phenotype with loss of glandular component in the xenografts. Epidermal growth factor receptor and SALL2 were expressed in primary tumors and xenografts. Enhanced bcl-2 and bax expression were noted in xenografts. Ki-67 overexpression in xenografts correlated with high mitotic index. Epithelial membrane antigen (EMA) and cytokeratin AE1/AE3 were detected in all original and xenografted SSs. Hierarchical clustering differentiated original MFSS and BSS, but their xenografts clustered together due to similar immunoexpression profile. Our study demonstrates definite phenotypic variability of BSS and MFSS in the xenografts. Differences in immunoexpression for various markers existed between primary tumor and xenografts but not between subtypes. Hierarchical clustering grouped TMA immunostaining data and confirmed immunophenotypic variability; however, it failed to reveal any immunophenotypic differences between SYT-SSX1 and SYT-SSX2 type tumors. Nonetheless, reverse-transcriptase-polymerase chain reaction detected SYT-SSX transcripts in all primary SSs and their xenografts, thereby demonstrating their genetic stability.
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PMID:Tissue microarray profiling of primary and xenotransplanted synovial sarcomas demonstrates the immunophenotypic similarities existing between SYT-SSX fusion gene confirmed, biphasic, and monophasic fibrous variants. 1695 34