Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.27.1 (RNase)
16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We isolated the Schizosaccharomyces pombe zfs1 gene as a multicopy suppressor of the sterility caused by overexpression of a double-stranded RNase. The deduced zfs1 gene product of 404 amino acids showed similarity to a mouse growth factor-inducible nuclear protein Nup475. Its C-terminal region carried two putative zinc-fingers, both of which should be intact for the protein to be functional as the suppressor. This protein appeared to localize in nuclei. Disruption of zfs1 was not lethal but conferred deficiency in mating and sporulation. Activation of transcription in response to the mating pheromone signaling was greatly reduced in the zfs1-disrupted cells. The mating deficiency of the zfs1-disruptant was suppressed partially by overexpression of either gpa1, ras1, byr1, or byr2, which are involved in the transmission of the pheromone signal. Disruption of zfs1 reduced both hypersensitivity of the ras1Val17 mutant to the mating pheromone and uncontrolled mating response caused by mutational activation of Gpa1, the G protein alpha subunit coupled to the mating pheromone receptors. However, overexpression of zfs1 could not bypass complete loss of function of either gpa1, ras1, byr1, or byr2. These observations indicate that the function of zfs1 is involved in the mating pheromone signaling pathway, and are consistent with its function being required to fully activate a factor in this pathway, either directly or indirectly.
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PMID:Schizosaccharomyces pombe zfs1+ encoding a zinc-finger protein functions in the mating pheromone recognition pathway. 853 15

WT1, a gene deleted in some Wilms' tumors, encodes a transcription factor with zinc fingers and shares homology with proteins in the early growth response gene family. Although defects in the WT1 gene are associated with nephroblastoma and genitourinary malformation, the specific function of WT1 in the gonads remains unclear. We investigated the expression of WT1 transcripts in rat ovary during follicle development by Northern blotting, RNase protection assay, and in situ hybridization. Abundant WT1 transcripts were found in the ovary, testis, uterus, and kidney, with lower levels in the heart and pancreas. Treatment with estrogen or gonadotropins did not affect the concentration of ovarian WT1 mRNA. In situ hybridization analysis indicated that ovarian WT1 mRNA is expressed exclusively in the surface epithelium and granulosa cells of primordial, primary, and secondary follicles, and its levels decrease during follicle growth. Although RNase protection assay suggested the presence of four alternatively spliced forms of WT1 mRNA, the ratio of these transcripts remains constant during ovarian growth. Developmental changes in the expression of two granulosa cell differentiation marker genes, inhibin-alpha and FSH receptor, were found to be inversely correlated with WT1 levels. Because potential WT1-binding sites were found in the promoter of inhibin-alpha gene, we further tested whether WT1 might regulate the expression of this gene. Cotransfection of a WT1 expression vector with a promoter reporter plasmid of inhibin-alpha resulted in the repression of promoter activities in CHO cells in a dose-dependent manner. These results suggest that WT1 is expressed in high levels in granulosa cells of primordial, primary, and secondary follicles but decreases with follicle development. This transcription factor might be a repressor of ovarian differentiation genes in the granulosa cells and play a role in arresting the differentiation of immature follicles.
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PMID:Wilms' tumor protein WT1 as an ovarian transcription factor: decreases in expression during follicle development and repression of inhibin-alpha gene promoter. 854 44

Complement component C4 is encoded by two nearly identical genes, C4A and C4B, that encode a C4 precursor that is proteolytically cleaved into the alpha, beta and gamma subunits of the mature protein. C4 is expressed primarily in liver and to a much lesser extent in immune cells. We have identified a unique 1 kb RNA transcript, termed Z, that arises from a cryptic promoter lying in the intron between exons 35 and 36 of the C4 gene. Primer extension, RNase protection, and 5' RACE experiments locate the cap site in intron 35, 55 bases upstream from exon 36. Northern blotting and RNase protection assays show that expression of this 1 kb Z RNA transcript is confined to the adrenal gland. Z RNA contains the same open reading frame as C4 which predicts a protein of 131 amino acids, but antisera to C4 do not interact with epitopes on this protein when it is synthesized by cell-free translation, hence the presence or absence of a Z protein in vivo could not be determined. Transfection of Z promoter/reporter constructs into human adrenal NCI-H295 cells shows that most if not all of the sequences required for high-level adrenal expression lie within 235 bases upstream from the cap site, but that this region is inactive when transfected into COS-1, JEG-3 and Hep-G2 cells, suggesting it contains an adrenal-specific element. The 222 bases upstream from the cap site are 75% identical in the human C4A and mouse Slp genes, and contain a potential binding site for steroidogenic factor 1 (SF-1), an orphan zinc-finger nuclear receptor. We propose that this region, like a nearby region in the mouse genome, functions as an upstream element of the P450c21 promoter, and may be a component of an adrenal-specific locus-control region.
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PMID:A promoter within intron 35 of the human C4A gene initiates abundant adrenal-specific transcription of a 1 kb RNA: location of a cryptic CYP21 promoter element? 858 88

Certain metal ions are known to be potent sensitizers, but the self proteins modified by metal ions and the self peptides recognized by 'metal-specific' T cells are unknown. In humans and mice treatment with gold anti-rheumatic drugs, containing Au(I), may lead to allergic and autoimmune side effects. Human and murine T cells do not react to Au(I), however, but to the reactive metabolite Au(III). Here we show that alteration by Au(III) of a model antigen, bovine ribonuclease (RNase)A, results in T cell sensitization to cryptic peptides of this protein. Upon immunization of mice with Au(III)-pretreated RNase [RNase/Au(III)], CD4+ T cell hybridomas specific for RNase/Au(III) were obtained in addition to those recognizing the immunodominant peptide RNase 74-88; the latter also were obtained after immunization with native RNase. RNase/Au(III)-specific T cell hybridomas reacted against RNase/Au(III) and RNase denatured by S-sulfonation of cysteine residues, but not against native RNase, or RNase pretreated with Au(I), A1(III), Cu(II), Fe(II), Fe(III), Ni(II), Mn(II), or Zn(II). Using a panel of overlapping, synthetic RNase peptides which were devoid of gold or gold-induced modifications, epitope mapping revealed that RNase/Au(III)-specific T cell hybridomas recognized the cryptic peptides 7-21 and 94-108, respectively. Comparison of the proliferative response of bulk CD4+ T cells, prepared from splenocytes after immunization with either RNase/Au(III) or native RNase, revealed that Au(III) pretreatment of RNase led to a markedly enhanced response to the two cryptic peptides while it did not influence the response to the immunodominant peptide. The cryptic peptides were also presented after preincubation of bone marrow-derived macrophages with RNase and Au(I), but not with RNase alone, suggesting that oxidation of Au(I) to Au(III) and subsequent protein alteration by Au(III) can happen in mononuclear phagocytes. We conclude that Au(III) alteration of proteins alters antigen processing and, thus leads to presentation of cryptic peptides. This mechanism may shed light on the development of allergic and autoimmune side effects of Au(I) anti-rheumatic drugs. In addition, it might provide a general mechanism of how metal ions act as T cell sensitizers.
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PMID:Alteration of a model antigen by Au(III) leads to T cell sensitization to cryptic peptides. 861 92

This paper describes the purification and properties of a 2',3'-cyclic nucleotide 3'-phosphodiesterase which hydrolyzes nucleoside 2',3'-cyclic monophosphates to nucleoside 2'-phosphates. The enzyme is present in encysted gastrulae of Artemia and its specific activity greatly increases during larval development. The purified enzyme has a molecular weight of around 55 000 as estimated by gel filtration, does not require metals for activity, is inhibited by Zn2+ and inactivated by Cu2+ and has a pH optimum at around neutrality. Based on the relative values of V(max)/Km, the specificity of the phosphodiesterase toward the four 2',3'-cyclic nucleotides is Guo-2',3'-P > Ado-2',3'-P > Cyd-2',3'-P > Urd-2',3'-P = 45:36:20:7. The enzyme from Artemia gastrulae is competitively inhibited by the four nucleosides 2'-phosphates (Ki values around 1 mM) while the enzyme from larvae is only inhibited by the purine nucleotides. The phosphodiesterase characterized in this work is more similar in substrate specificity to the 2',3'-cyclic nucleotide 3'-phosphodiesterase from the mammalian nervous system than to the plant enzyme. The functional relationship of this enzyme with the Artemia ribonuclease VI is discussed.
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PMID:Purification and characterization of Artemia 2',3'-cyclic nucleotide 3'-phosphodiesterase. 864 16

The allergic pig can be used as a large-animal model for studies of allergic reactions in the airways and the role of eosinophils in such reactions. To measure the activation of eosinophils, the release of eosinophil-derived cationic proteins can be used. The purpose of this study was to isolate and characterize cationic proteins derived from porcine eosinophils. Pigs were infested with live Ascaris suum eggs to induce eosinophilia (greater than or = 40% of leukocytes). Blood was collected and leukocytes were prepared by dextran sedimentation. Granules were obtained from the homogenized leukocytes by ultracentrifugation and cationic proteins were extracted and separated by gel filtration, cation exchange and zinc affinity chromatography. Using these methods, three cationic proteins were isolated from pig granulocytes, two of which were shown to originate from the eosinophil. The proteins were characterized according to molecular weight, amino acid composition, N-terminal sequence, isoelectric point, peroxidase and ribonuclease activity and antigenicity. One eosinophil protein was identified as eosinophil peroxidase and the other showed great similarities with human eosinophil cationic protein. The third protein was not specific for eosinophils, and had no obvious equivalent in human granulocytes. The eosinophil-derived proteins may be useful in the studies of eosinophil activation, e.g. in late-phase asthmatic reactions, where the pig represents a new candidate model for large-animal allergy research.
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PMID:Isolation and characterization of porcine cationic eosinophil granule proteins. 864 90

We have isolated a mouse ATBF1 cDNA which is 12-kb long and capable of encoding a 406-kDa protein containing four homeodomains and 23 zinc-finger motifs. Mouse ATBF1 is 94% homologous to the human ATBF1-A transcription factor. Northern blot and RNase protection analysis showed that levels of ATBF1 transcripts were low in adult mouse tissues, but high in developing brain, consistent with a role for ATBF1 in neuronal differentiation.
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PMID:Cloning of the cDNA encoding the mouse ATBF1 transcription factor. 865 49

We recently reported that GS-X pump activity, as assessed by ATP-dependent transport of the glutathione-platinum complex and leukotriene C4, and intracellular glutathione (GSH) levels were remarkably enhanced in cis-diamminedichloroplatinum(II) (cisplatin)-resistant human leukemia HL-60 cells (Ishikawa, T., Wright, C. D., and Ishizuka, H. (1994) J. Biol. Chem. 269, 29085-29093). Now, using Northern hybridization and RNase protection assay, we provide evidence that the multidrug resistance-associated protein (MRP) gene, which encodes a human GS-X pump, is expressed at higher levels in cisplatin-resistant (HL-60/R-CP) cells than in sensitive cells, whereas amplification of the MRP gene is not detected by Southern hybridization. Culturing HL-60/R-CP cells in cisplatin-free medium resulted in reduced MRP mRNA levels, but these levels could be induced to rise within 30 h by cisplatin and heavy metals such as arsenite, cadmium, and zinc. The increased levels of MRP mRNA were closely related with enhanced activities of ATP-dependent transport of leukotriene C4 (LTC4) in plasma membrane vesicles. The glutathione-platinum (GS-Pt) complex, but not cisplatin, inhibited ATP-dependent LTC4 transport, suggesting that the MRP/GS-X pump transports both LTC4 and the GS-Pt complex. Expression of gamma-glutamylcysteine synthetase in the cisplatin-resistant cells was also co-induced within 24 h in response to cisplatin exposure, resulting in a significant increase in cellular GSH level. The resistant cells exposed to cisplatin were cross-resistant to melphalan, chlorambucil, arsenite, and cadmium. These observations suggest that elevated expression of the MRP/GS-X pump and increased GSH biosynthesis together may be important factors in the cellular metabolism and disposition of cisplatin, alkylating agents, and heavy metals.
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PMID:Coordinated induction of MRP/GS-X pump and gamma-glutamylcysteine synthetase by heavy metals in human leukemia cells. 866 1

The mouse Zic genes encode zinc-finger (Zf) proteins expressed only in the cerebellum of the adult brain. The genes are the vertebrate homologues of the Drosophila pair-rule gene, odd-paired (opa). We identified a novel gene, Zic4, which belongs to the Zic gene family, through a genomic and cDNA cloning study. Zic4 is highly similar to Zic1, Zic2 and Zic3, especially in its Zf motif. An analysis of the genomic organization of Zic4 showed that the gene shares a common exon-intron boundary with Zic1, Zic2, Zic3 and opa. The chromosomal location of Zic4 was determined to be mouse chromosome 9 in the vicinity of Zic1, using an interspecific backcross panel. An RNase protection study showed that Zic4 is expressed only in the cerebellum during the adult stage, as are the other Zic genes. The temporal profile of mRNA expression in the developing cerebellum is similar to that of Zic3 which has a peak on postnatal day 5. These findings suggest that Zic4 is a gene which works cooperatively with other Zic genes during cerebellar development.
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PMID:Identification and characterization of Zic4, a new member of the mouse Zic gene family. 868 19

The Wilms tumor suppressor gene WT1 is implicated in the ontogeny of genito-urinary abnormalities, including Denys-Drash syndrome and Wilms tumor of the kidney. WT1 encodes Kruppel-type zinc finger proteins that can regulate the expression of several growth-related genes, apparently by binding to specific DNA sites located within 5' untranslated leader regions as well as 5' promoter sequences. Both WT1 and a closely related early growth response factor, EGR1, can bind the same DNA sequences from the mouse gene encoding insulin-like growth factor 2 (Igf-2). We report that WT1, but not EGR1, can bind specific Igf-2 exonic RNA sequences, and that the zinc fingers are required for this interaction. WT1 zinc finger 1, which is not represented in EGR1, plays a more significant role in RNA binding than zinc finger 4, which does have a counterpart in EGR1. Furthermore, the normal subnuclear localization of WT1 proteins is shown to be RNase, but not DNase, sensitive. Therefore, WT1 might, like the Kruppel-type zinc finger protein TFIIIA, regulate gene expression by both transcriptional and posttranscriptional mechanisms.
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PMID:RNA binding by the Wilms tumor suppressor zinc finger proteins. 875 14


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