Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intron-encoded U17a and U17b RNAs are members of the H/ACA-box class of small nucleolar RNAs (snoRNAs) participating in rRNA processing and modification. We have investigated the organization and expression of the U17 locus in human cells and found that intronic U17a and U17b sequences are transcribed as part of the three-exon transcription unit, named U17HG, positioned approximately 9 kb upstream of the RCC1 locus. Comparison of the human and mouse U17HG genes has revealed that snoRNA-encoding intron sequences but not exon sequences are conserved between the two species and that neither human nor mouse spliced U17HG poly(A)+ RNAs have the potential to code for proteins. Analyses of polysome profiles and effects of translation inhibitors on the abundance of U17HG RNA in HeLa cells indicated that despite its cytoplasmic localization, little if any U17HG RNA is associated with polysomes. This distinguishes U17HG RNA from another non-protein-coding snoRNA host gene product, UHG RNA, described previously (K. T. Tycowski, M. D. Shu, and J. A. Steitz, Nature 379:464-466, 1996). Determination of the 5' terminus of the U17HG RNA revealed that transcription of the U17HG gene starts with a C residue followed by a polypyrimidine tract, making this gene a member of the 5'-terminal oligopyrimidine (5'TOP) family, which includes genes encoding ribosomal proteins and some translation factors. Interestingly, other known snoRNA host genes, including the UHG gene (Tycowski et al., op. cit.), have features of the 5'TOP genes. Similar characteristics of the transcription start site regions in snoRNA host and ribosomal protein genes raise the possibility that expression of components of ribosome biogenesis and translational machineries is coregulated.
Mol Cell Biol 1998 Aug
PMID:The host gene for intronic U17 small nucleolar RNAs in mammals has no protein-coding potential and is a member of the 5'-terminal oligopyrimidine gene family. 967 60

We applied a differential cloning procedure, the in-gel competitive reassociation (IGCR) method, to clone altered genomic sites from the whole genomes of renal cell carcinoma cells. After four rounds of IGCR, we obtained from two patients libraries enriched 1000- and 2500-fold for differential DNA fragments specific to allelic changes in renal cell carcinoma. In these libraries, we found differential fragments of single-copy sequences as well as repetitive sequences. The fragments exhibited allelic loss, restriction-fragment-length polymorphism, size changes, and changes in the copy number, and common allelic losses were also detected in the cancer tissues from several renal cell carcinoma patients. Some of the clones showed changes in the repeat length of microsatellites. One third (seven of 22) of the clones exhibiting these changes were mapped to chromosomes 8 or 9. Decreases in the copy numbers of mitochondrial DNA and satellite I were observed in 13 of 17 and seven of 16 renal cell carcinoma patients, respectively. This suggests that the IGCR method can be used to clone DNA fragments with various structural changes from the whole genomes of cancer tissues.
Mol Carcinog 1998 Jul
PMID:A whole-genome analysis of allelic changes in renal cell carcinoma by in-gel competitive reassociation. 968 41

Gene amplification, which has often been observed in various human cancers, appears to be associated with the development and progression of malignant phenotypes. However, in renal cell carcinoma (RCC), conventional analytic methods requiring specific primers and probes have revealed infrequent amplification of known oncogenes. We attempted to determine if gene amplification was truly uncommon in RCC. The genomic DNAs extracted from 5 human RCC cell lines were examined by restriction landmark genomic scanning (RLGS), a two-dimensional gel analysis which allows evaluation of approximately 2,000 radiolabelled DNA fragments. By this method, we detected 24 distinct spots commonly amplified in at least 2 RCC cell lines compared to normal kidneys. Comparing the present results with chromosomal assigned-RLGS, approximately one half of these DNA fragments proved to be located on chromosome 2, 5 or 7. Our data suggest that amplification of unknown genes is likely to occur in RCC cell lines.
Cell Mol Biol (Noisy-le-grand) 1998 Sep
PMID:Detection of DNA amplification in human renal cell carcinoma cell lines using restriction landmark genomic scanning. 976 94

Twenty nine hybrids retaining fragments of human chromosome 2 were characterized by reverse-FISH and by a panel of 106 STSs. Most of the hybrids are radiation hybrids retaining fragments of chromosome 2 as the only human contribution. The hybrid panel dissected chromosome 2 in 69 distinct physical regions, allowing a fine mapping of the sequences. These hybrids are particularly useful as starting points for generation, via Alu-PCR, of specific partial chromosome paints (PCP). We also report the mapping by FISH of 60 YACs located on chromosome 2. These resources can be advantageously used in cytogenetic investigations, with particular reference to cancer cytogenetics, as illustrated with the renal carcinoma cell line KRC/Y.
Somat Cell Mol Genet 1998 Jan
PMID:A panel of partial chromosome paints and YAC probes specific for human chromosome 2. 977 78

We investigated the expression of MAGE genes in 10 renal cell carcinoma (RCC) cell lines, 50 RCC tumor samples and 5 normal kidney samples using reverse transcription-polymerase chain reaction (RT-PCR). MAGE-1, -2, -3 and -4 genes were expressed in 4, 1, 10 and 3 of 10 RCC cell lines, respectively, and 11, 8, 38 and 15 of 50 RCC samples. In contrast, there was no expression of MAGE genes detected in any of the normal kidneys. The incidence of the expression of plural MAGE genes in high stage RCC was significantly higher than that in low stage RCC. An analysis based on clinicopathological factors revealed that MAGE-4 gene was more frequently expressed in clear cell subtype than in granular cell subtype RCCs. Our results suggest that owing to the high incidence of MAGE gene expression in RCC, a large proportion of patients could be suitable candidates for novel immune therapies involving tumor-specific antigens encoded by MAGE genes.
Int J Mol Med 1998 Jul
PMID:Expression of MAGE genes in renal cell carcinoma. 985 43

The regulatory mechanisms responsible for malignant transformation, tumor progression and metastasis in renal cell cancer (RCC) are still unclear, but there is some evidence that biologically active peptides might have regulatory effects on the behavior of this malignancy. Tumor cells can change local concentrations of active peptides by modulating their cell-surface enzymes. Using immunohistochemistry and enzyme-histochemistry, the expression of various membrane peptidases was examined in RCC and adjacent noninvaded renal parenchyma (n = 44). We describe the down-regulation of neutral endopeptidase 24.11 (NEP) protein expression in RCC of the clear cell/chromophilic type when compared with renal parenchyma, and show for the first time the lack of enzyme activity of NEP in RCC. The strongest expression could be found for dipeptidyl peptidase IV (DPIV) which is only decreased in RCC of the chromophobe cell type and is even present in oncocytoma. Aminopeptidase N (APN) and aminopeptidase A (APA) show attenuated expression in up to one third of clear cell/ chromophilic RCC. Chromophobe RCC and oncocytomas do not express APN, APA, NEP and gamma-glutamyltranspeptidase.
Int J Mol Med 1998 Oct
PMID:Endopeptidase 24.11/CD10 is down-regulated in renal cell cancer. 985 25

Panax ginseng roots have long been used as a medicinal herb in oriental countries. We have investigated anti-proliferative effects of lipid soluble Panax ginseng components on human renal cancer cell lines. Petroleum ether extract of Panax ginseng roots (GX-PE) or its partially purified preparation (7:3 GX) was added to cultures of three human renal cell carcinoma (RCC) cell lines, A498, Caki-1, and CURC II. Proliferation of RCC cells was estimated by a [3H]thymidine incorporation assay and cell cycle distribution was analyzed by flow cytometry. GX-PE, 7:3 GX, panaxydol and panaxynol inhibited proliferation of all three RCC cell lines in a dose dependent manner in vitro with an order of potency, 7:3 GX > panaxydol > panaxynol = GX-PE. Additive effect of interleukin 4 was also demonstrated, most prominently in Caki-1 which responded poorly to GX-PE alone. Analysis of cell cycle in CURC II and Caki-1 treated with GX-PE demonstrated increase in G1 phase population and corresponding decrease in S phase population. The present study demonstrated that proliferation of human RCC cell lines were inhibited by lipid soluble components of Panax ginseng roots by blocking cell cycle progression at G1 to S phase transition.
Exp Mol Med 1998 Mar 31
PMID:Effect of petroleum ether extract of Panax ginseng roots on proliferation and cell cycle progression of human renal cell carcinoma cells. 987 22

The absence of functional von Hippel-Lindau (VHL) tumor suppressor gene leads to the development of neoplasias characteristic of VHL disease, including renal cell carcinoma (RCC). Here, we compared the sensitivity of RCC cells lacking VHL gene function with that of RCC cells expressing the wild-type VHL gene (wtVHL) after exposure to various stresses. While the response to most treatments was not affected by the VHL gene status, glucose deprivation was found to be much more cytotoxic for RCC cells lacking VHL gene function than for wtVHL-expressing cells. The heightened sensitivity of VHL-deficient cells was not attributed to dissimilar energy requirements or to differences in glucose uptake, but more likely reflects a lesser ability of VHL-deficient cells to handle abnormally processed proteins arising from impaired glycosylation. In support of this hypothesis, other treatments which act through different mechanisms to interfere with protein processing (i.e., tunicamycin, brefeldin A, and azetidine) were also found to be much more toxic for VHL-deficient cells. Furthermore, ubiquitination of cellular proteins was elevated in VHL-deficient cells, particularly after glucose deprivation, supporting a role for the VHL gene in ubiquitin-mediated proteolysis. Accordingly, the rate of elimination of abnormal proteins was lower in cells lacking a functional VHL gene than in wtVHL-expressing cells. Thus, pVHL appears to participate in the elimination of misprocessed proteins, such as those arising in the cell due to the unavailability of glucose or to other stresses.
Mol Cell Biol 1999 Feb
PMID:Protective function of von Hippel-Lindau protein against impaired protein processing in renal carcinoma cells. 989 Oct 63

The von Hippel-Lindau (VHL) tumour suppressorgene product is believed to be involved in the down-regulation of transcriptional elongation by preventing the association of elongin B and C with the catalytic subunit elongin A. Alterations in the human VHL gene lead to VHL disease which is associated with various rare neoplasias, including haemangioblastoma of the central nervous system, retinal angioma, clear cell renal carcinoma and pheochromocytoma. Recently, a protein (VBP1) was isolated that was found to bind to the VHL protein in vivo. We have used the murine Vbp1 homologous cDNA to investigate the expression of the Vbp1 mRNA in the mouse by in situ hybridization and northern blot analysis. In fetal stages between days 9 and 18 of gestation, Vbp1 was expressed mainly in the central nervous system, retina and liver. In addition, at day 12, high expression was observed in the labyrinthine region of the placenta. In later stage placentas, Vbp1 expression was, however, considerably reduced. Northern blot analysis of adult mouse tissues showed that Vbp1 was ubiquitously expressed. In situ analysis on several adult tissues showed that in most tissues, transcripts were evenly distributed. In brain, eye, kidney and intestine, however, Vbp1 was expressed in specific cell types. Moreover, expression of the human VBP1 gene was investigated in cerebellum and in various tumours of VHL patients encompassinghaemangioblastomas, renal cell carcinomas and pheochromocytomas. In all of these tissues, VBP1 was ubiquitously expressed at low levels. However, no consistent differences in VBP1 expression levels could be detected between tumours and normal tissue. Mapping of the murine Vbp1 gene revealed conserved chromosomal localization between mouse and human in a region homologous to human Xq28.
Hum Mol Genet 1999 Feb
PMID:Expression of the von Hippel-Lindau-binding protein-1 (Vbp1) in fetal and adult mouse tissues. 993 30

The nuclear accumulation of beta-catenin plays an important role in the Wingless/Wnt signaling pathway. This study describes an examination of the nuclear import of beta-catenin in living mammalian cells and in vitro semi-intact cells. When injected into the cell cytoplasm, beta-catenin rapidly migrated into the nucleus in a temperature-dependent and wheat germ agglutinin-sensitive manner. In the cell-free import assay, beta-catenin rapidly migrates into the nucleus without the exogenous addition of cytosol, Ran, or ATP/GTP. Cytoplasmic injection of mutant Ran defective in its GTP hydrolysis did not prevent beta-catenin import. Studies using tsBN2, a temperature-sensitive mutant cell line that possesses a point mutation in the RCC1 gene, showed that the import of beta-catenin is insensitive to nuclear Ran-GTP depletion. These results show that beta-catenin possesses the ability to constitutively translocate through the nuclear pores in a manner similar to importin beta in a Ran-unassisted manner. We further showed that beta-catenin also rapidly exits the nucleus in homokaryons, suggesting that the regulation of nuclear levels of beta-catenin involves both nuclear import and export of this molecule.
Mol Biol Cell 1999 Apr
PMID:beta-catenin can be transported into the nucleus in a Ran-unassisted manner. 1019 61


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