Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Okadaic acid, dinophysistoxin-1 (35-methylokadaic acid), and calyculin A are the okadaic acid class of non-12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters, which do not bind to the phorbol ester receptors in cell membranes or activate protein kinase C in vitro. They have potent tumor-promoting activities on mouse skin, as strong as TPA-type tumor promoters, such as TPA, teleocidin, and aplysiatoxin. DNA samples isolated from tumors induced by dimethylbenz[alpha]anthracene and each of the okadaic acid class tumor promoters had the same mutation at the second nucleotide of codon 61 (CAA to CTA) in the c-H-ras gene. Okadaic acid receptors, protein phosphatases 1 and 2A, are present in the particulate as well as cytosolic fractions of various mouse tissues. The apparent "activation" of protein kinases by the okadaic acid class tumor promoters, after their incubation with 32P-ATP, protein kinases, and protein phosphatases, was observed. This activation was caused by inhibition of protein phosphatases 1 and 2A by the okadaic acid class tumor promoters. Treatment of primary human fibroblasts and human keratinocytes with the okadaic acid class tumor promoters induced the hyperphosphorylation of a 60-kDa protein in nuclear and cytosolic fractions, due to the inhibition of protein phosphatases. The 60-kDa protein is a proteolytic fragment of nucleolin, a major nonhistone protein and is designated as "N-60." The mechanisms of action of the okadaic acid class tumor promoters are discussed with emphasis on the inhibition of protein phosphatase activity.
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PMID:Mechanisms of action of okadaic acid class tumor promoters on mouse skin. 166 50

The four D-2-amino-4,5-methano-adipates 26, 27, 32, 33 were synthesized and their biological activity at the N-methyl-D-aspartate (NMDA) receptor was assessed. The synthesis involved as a key step a rhodium acetate dimer catalyzed addition of ethyl diazoacetate to the protected D-allylglycine (17). In vitro receptor binding using L-[3H]glutamate as the radioligand provided affinity data, while modulation of [3H]TCP binding was used as a functional assay. The analogues were also evaluated in [3H]kainate and [3H]AMPA binding to assess selectivity over non-NMDA glutamate receptors. Three of the four diastereoisomer, D-CAA B (27), C (32) and D (33) were shown to have agonist properties at the NMDA-site, while the fourth, (2R,4R,5R) D-CAA A (26) was characterized as an NMDA-site atypic antagonist.
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PMID:Synthesis, absolute configuration and activity at N-methyl-D-aspartic acid (NMDA) receptor of the four D-2-amino-4,5-methano-adipate diastereoisomers. 166 58

The presence of ubiquitin in ciliates was first demonstrated in Tetrahymena pyriformis. One clone--pTU2--presents two incomplete open reading frames and the putative polyubiquitin genes have been shown to be highly similar to those of other organisms. To further analyze the organization of this multigene family, several fragments of macronuclear DNA were cloned. We report here the isolation and characterization of one genomic clone (pTU20) that encodes a polyubiquitin gene (TU20) with five tandem repeats and presenting only one extra triplet CAA (Gln) upstream from the TGA. The promoter region of TU20 also presents a consensus heat shock element. The specific detection of RNA species with a synthetic oligonucleotide probe reveals that it corresponds to the 1.8 kb mRNA species whose expression is increased by temperature stress.
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PMID:The macronuclear polyubiquitin gene of the ciliate Tetrahymena pyriformis. 166 85

Southern blot hybridization was performed with probe v-erbB + A in 4 subjects. Two of them were patients with similar erythroid alterations of bone marrow: one of them was diagnosed as erythroleukemia (EL). The other two were members of a same family (husband and wife). The husband had normal erythroid cellularity of bone marrow but the wife and their 7 living sons and daughters had erythroid hypercellularity. In the second generation of this family 4 hematological patients (1 with AML and 3 with CAA) were found in the past decade. Rearrangement of cerbB and c-erbA genes was found in 3 of the 4 subjects (2 with EL and the wife mentioned above). They had 4 new hybridization bands besides 3 germlines, but the husband had only 3 germlines. The result suggests that using Southern blot hybridization technique with probe v-erbB + A, the rearrangement of c-erbB/c-erbA genes might be a diagnostic indicator of erythroleukemia at early stage of leukomogenesis in familial and sporadic patients. The etiological significance of the rearrangement of c-erbB/c-erbA in leukomogenesis was discussed.
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PMID:[Gene diagnosis of familial erythroleukemia at the early stage of leukomogenesis]. 168 Jun 13

Twenty-nine patients with acute myelocytic leukemia (AML) and 14 patients with Philadelphia chromosome-positive chronic myelocytic leukemia (CML) were analyzed to detect the presence of mutations in their ras genes by the polymerase chain reaction and oligonucleotide hybridization methods. Deoxyribonucleic acid (DNA) isolated from blood or bone marrow samples was screened for mutations in codons 12, 13 and 61 of N-ras and in codons 12 and 61 of K-ras and H-ras. We detected mutations of the ras gene in 7 patients with AML (7/29), all in N-ras. The mutations were 3 GGT- greater than GAT transitions in codon 12, 1 GGT- greater than TGT transition in codon 13, and 3 CAA- greater than AAA transitions in codon 61. No correlation has been observed between French-American-British subtypes and the incidence of N-ras mutation, nor between cytogenetic changes and the incidence of N-ras mutation. All ras gene mutations detected by the oligonucleotide hybridization method were further confirmed by direct sequencing. No mutations were detected in ras genes in samples from the 14 Philadelphia chromosome-positive CML patients (12 in chronic phase, 2 in blastic phase). These findings are in line with previous results indicating that ras gene mutations in the codons tested play only a small role in the tumorigenesis of CML.
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PMID:Mutation analysis of the ras gene in myelocytic leukemia by polymerase chain reaction and oligonucleotide probes. 168 80

The 5' start sites and the 3' ends of giant transcripts of the approximately 20-kilobase (kb)-long chicken alpha-globin gene domain were identified by reverse transcription with specific primers and by nuclease S1 mapping using cloned and sequenced restriction fragments of the domain. A transcriptional unit of approximately 17 kb was found that includes all three embryonic and adult genes of the cluster. The largest transcript initiates 8 kb upstream of the gene, within a cluster of A + T-rich sequences placed upstream of a matrix attachment point, at one of several CAA(A)T boxes framing a cluster of four TATA boxes. The 5' ends of a group of 2.5-, 5-, and 12-kb globin transcripts accumulating in avian erythroblastosis virus-transformed cells, which transcribe globin genes abortively, map to the sequence ATATATAATAA 1 kb upstream of the embryonic pi-globin gene. This sequence might correspond to a site of RNA processing or of alternative transcription initiation. Transcription of the domain ends about 2 kb downstream of the last gene of the cluster, downstream of an enhancer and immediately upstream of a CR1 repetitive element in an A + T-rich sequence that includes a matrix attachment site. These data indicate that full-domain transcripts including embryonic as well as adult alpha-globin genes exist, and that the region transcribed is framed by A + T-rich linkers and matrix attachment points.
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PMID:The chicken alpha-globin gene domain is transcribed into a 17-kilobase polycistronic RNA. 168 44

10 derivations of rat tracheal epithelial (RTE) cells, including normal cells, normal primary cultures, 7 tumorigenic cell lines and 1 nontumorigenic cell line transformed in vitro by treatment with 7,12-dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene (BP) and/or 12-O-tetradecanoylphorbol-13-acetate (TPA) were examined for oncogene alterations. No abnormalities of Ha-ras or Ki-ras were seen that were suggestive of amplification, rearrangement or the presence of RFLPs. Analysis of specific-point mutations in Ha-ras using Pst I digestion (codon 12, GGA to GCA) or Ha-ras and Ki-ras using Xba I (codon 61, CAA to CTA) were negative. In one cell line derived by DMBA treatment, changes in the c-myc restriction digest pattern were seen after incubation with Bam HI and Hind III. Northern analysis revealed consistent differences between normal and transformed cells when probed with Ha-ras; c-myc expression was of low intensity, and the expression of Ki-ras could not be detected. Transfection of RTE cell DNAs into NIH/3T3 cells did not result in the appearance of morphologic transformants. The studies suggest that Ha-ras or Ki-ras codon 61 A to T transversions (CAA to CTA) are not associated with the immortal/tumorigenic phenotype in RTE cells transformed by DMBA or TPA, and are in contrast to results reported in some other biological systems.
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PMID:Oncogene alterations in in vitro transformed rat tracheal epithelial cells. 169 45

Two different molecular weight forms of apoB are produced from a common initial transcript via editing of a Gln codon (CAA) to a stop codon (UAA), leading to a truncated translation product (apo BS) that consists of the amino terminal half of the larger form (apoBL). Previous studies have shown that fasting coordinately decreases lipogenesis and the secretion of very low density lipoprotein (VLDL) lipids and apoBS. Secretion of the apoBL is unaffected by fasting. We studied whether editing of apoB RNA is repressed by fasting, thus accounting for the selective decreased secretion of apoBS. Column chromatography of [35S]methionine-labeled lipoproteins secreted by hepatocytes from fed rats showed that essentially all of apoBL is secreted in the VLDL fraction, whereas a significant amount (15%) of apoBS is secreted associated as lipoproteins eluting in the HDL fractions. Fasting decreased the relative amount of apoBS that eluted in the VLDL fractions and increased the amount secreted in the HDL fractions. Consistent with previous results, hepatocytes from fasted rats show a selective twofold decrease in apoBS secretion. Fasting did not affect the relative abundance of apoB RNA, determined by slot blot hybridization assays using two different 32P-labeled cDNA probes coding either for both molecular weight forms or for only the large molecular weight form. However, quantitative of the editing of apoB RNA showed that fasting caused a 60% decrease in the amount of apoB RNA possessing the stop codon. These data show that the editing of apoB RNA is sensitive to metabolic state (i.e., fasting) resulting in a selective decrease in the secretion of apoBS. However, since the total secretion of apoB was decreased by fasting, while apoB mRNA levels remained constant, additional (post-transcriptional) mechanisms play a role in regulating apoB secretion.
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PMID:Fasting decreases apolipoprotein B mRNA editing and the secretion of small molecular weight apoB by rat hepatocytes: evidence that the total amount of apoB secreted is regulated post-transcriptionally. 170 Oct 4

When a single RNA sequence is read in either the 5'-3' or 3'-5 direction, the translated peptides often are hydropathically similar even though their sequences may be different. To investigate whether hydropathically similar peptides might also be antigenically related, two peptides were synthesized from the substance P anti-sense RNA transcript: CAU CAA UCC AAA GAA CUG CUG AGG CUU GGG UCG. Translation of this RNA in the 5'-3' direction and in the 3'-5' direction resulted in two different peptides. HQSKELLRLGS and AGFGVVKKPNY, respectively. As anticipated, both peptides shared similar hydropathic profiles but were quite different with respect to their sequences. To examine their antigenic relatedness, mice were immunized with either peptide, and monoclonal antibodies were produced. Using an enzyme-linked immunosorbent assay, it was possible to demonstrate that the majority of monoclonal antibodies, selected for reactivity against the original immunogen, also reacted with the other peptide. The observed binding was determined to be specific since reactivity could be blocked with either soluble peptide. Thus, we demonstrate that hydropathically similar peptides obtained from the same RNA but translated in opposite directions are antigenically related despite difference in amino acid sequences.
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PMID:5'-3' and 3'-5' translation of the same RNA results in hydropathically similar peptides that are antigenically related. 170 18

The authors investigated by immunohistochemical study the drainage of three tumor-associated antigens in unaffected regional lymph nodes of colon cancer patients. The study was conducted using monoclonal antibodies (MoAb) directed against different epitopes of the tumor-associated glycoprotein, TAG-72 (CC-49, CC-83, B72.3), of the carcinoembryonic antigen (CEA) (COL-4, COL-12), and of the colon-associated antigen, CAA (anti-CAA). The authors detected immunohistochemical reactions of MoAb CC-49 and anti-CAA with antigen-presenting cells (APC), such as peritumoral and sinus macrophages and lymphatic endothelial cells and with specific areas of germinal centers in lymph nodes draining 11 of 24 colorectal carcinomas studied. The corresponding primary tumors expressed the TAG-72 and CAA antigens. No immunostaining was detectable in lymph nodes using the anti-CEA MoAb, even when the primary tumors strongly expressed the specific epitopes. In germinal centers of regional lymph nodes, the immunostaining was often distributed at the periphery with a characteristic crescentic or circular pattern, which strongly suggested the exposure of the specific epitopes defined by MoAb CC-49 and anti-CAA on follicular dendritic cells. This would indicate that these epitopes are selectively recognized and presented to germinal center B-cells. This phenomenon may have clinical and diagnostic implications.
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PMID:Immunohistochemical evidence of immune responses to tumor-associated antigens in lymph nodes of colon carcinoma patients. 170 62


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