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)

Rat hepatoma McA-RH7777 cell lines transfected with full-length human apolipoprotein (apo) B constructs produce mostly human apoB48 and only small amounts of apoB100, as a result of mRNA editing at codon 2153 (C to U conversion at nucleotide 6666). To abolish the formation of apoB48 and increase the yield of apoB100 and other forms of apoB longer than apoB48, site-specific mutations were introduced at or near the site of apoB mRNA editing. Among four mutations examined, only that in which codon 2153 was converted from CAA (Gln) to CTA (Leu) effectively precluded the formation of apoB48. In this mutant, a stop codon would not be generated even if the C to U conversion occurred. The three other mutations were introduced to disrupt the proposed stem-loop structure encompassing the editing site. Changes made in the third positions of five codons on the 5' side of the edited base or of four codons 3' of the edited base failed to eliminate the production of a protein with the approximate size of apoB48. A construct in which codon 2153 was changed from CAA to GAT (Asp) also failed to eliminate the production of a protein the size of apoB48. Analysis of the region between nucleotides 6200 and 6900 of the cDNA did not detect any prevalent alternate editing sites. Immunoblot analysis using polyclonal antibodies raised against synthetic peptides of human apoB100 indicated that the carboxyl terminus of the apoB48-like proteins probably resides between amino acid residues 2068 and 2129 of apoB100. These results provide some insight into the mechanism of apoB mRNA editing and will facilitate further studies on apoB-containing lipoproteins.
 ...
PMID:Elimination of apolipoprotein B48 formation in rat hepatoma cell lines transfected with mutant human apolipoprotein B cDNA constructs. 173 Jun 41

We have shown previously that 48 base pairs (bp) of 5'-flanking sequence are necessary for correct initiation at the major transcriptional start site of the Chinese hamster dihydrofolate reductase (dhfr) gene (Ciudad et al., 1988). As an upstream element, this sequence alone confers 25% of maximum promoter activity. The 5' half of this sequence is particularly well conserved among mammalian species; it contains one Sp1 binding site (GC box) and one CAA element. In the present work, we have analyzed the role of this region by extensive point mutational analysis. Twenty-three dhfr minigene constructs containing 1- or 2-base substitutions in this region of the promoter were tested by measuring their ability to transfect DHFR-deficient Chinese hamster ovary cells to a DHFR+ growth phenotype. Eight mutants, all in or near the GC box, exhibited reduced transfection efficiency. Promoter disfunction in these mutants was confirmed by RNase protection analysis of stable transfectants. Gel retardation experiments showed that mutants affected in the consensus sequence for Sp1 binding were deficient in binding a protein found in nuclear extracts of Chinese hamster ovary cells. Purified human transcription factor Sp1 was also unable to bind a promoter sequence bearing one of these single base substitutions, suggesting that Sp1 itself is involved in dhfr transcription in vivo. We conclude that most single base mutations in the GC box severely cripple or eliminate promoter function by inhibiting binding of transcription factors to this regulatory sequence and that Sp1 is likely to be involved in dhfr transcription in vivo. We also found that the well conserved CAA element is not absolutely necessary for transcription.
 ...
PMID:Point mutational analysis of the hamster dihydrofolate reductase minimum promoter. 174 Apr 17

The carcinogenic properties of N-nitroso compounds are associated with their ability to alkylate DNA, in particular to form O6-alkylguanine and O4-alkylthymine. DNA duplexes containing either O6-alkylguanine or O4-alkylthymine were synthesized, and each duplex was ligated to form a set of DNAs of increasing length with the alkylated base out of phase (16 base-pairs apart) or in phase (21 base-pairs apart) with the helical repeat of the DNA. The DNA contained the sequence 5' CAA 3', which is the 61st codon of the K-ras gene, because this codon is a preferred site of mutation for a number of carcinogens including the methylating carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK). O4-Methylthymine or O4-ethylthymine replaced thymine in either of the two A.T base-pairs of this codon (normally CAA), and O6-methylguanine replaced the guanine in the G.C pair. All the sequences containing O4-alkylthymine exhibited anomalous, slow, gel migration and ligated to form circles of unusually small diameter. In general, the effect was seen when the alkylated base-pair was out of phase with the helical repeat as well as when it was in phase, suggesting that the alkylated base-pair confers flexibility which is largely isotropic, i.e., has no preferred direction, rather than anisotropic flexibility or bending. However, at pH 8.3 the 21-base-pair set containing O4-alkylT.A had significantly greater anomalous migration than the 16-base-pair set, suggesting that the flexibility produced by this base-pair has a significant anisotropic component and thus resembles true bending.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Nitrosamine-induced cancer: O4-alkylthymine produces sites of DNA hyperflexibility. 175 91

The spontaneous course of 58 patients with compensated autonomous adenoma of the thyroid was followed. Scintigraphic appearance (compensated (CAA) or decompensated (DAA)) was documented and the serum levels of thyroxine (T4), triiodothyronine (T3) and thyroid-stimulating hormone after TSH-stimulating hormone were measured at the beginning of observation and 3.8 years (median) later. During follow-up period, 13 patients (22%) with CAA developed DAA. 9/13 patients (15%) had overt hyperthyroidism with elevated T4 and/or T3 levels, 4/13 patients (7%) had normal thyroid hormone levels. Life table analysis showed a risk for developing hyperthyroidism of 19% at five years. The size of all adenomata measured scintigraphically was increasing during follow-up, and there was no discrimination of CAA from DAA using this technique. Eight CAA patients received iodinated contrast medium but none develop DAA. In conclusion from these results as well as from the literature, there is no indication for surgery or radioiodine therapy of patients with a CAA, even if there are plans to administer iodinated contrast medium.
 ...
PMID:[The spontaneous course of compensated autonomous thyroid gland adenomas]. 176 84

Blood from 48 chicks was examined for anemia (packed cell volume), and plasma was examined for virus particles by direct transmission electron microscopy (DTEM). There was agreement between the occurrence of anemia and the presence of CAA virus particles in plasma from anemic chicks (Kappa = 0.2425, Z = 2.096, P = 0.036). Although DTEM is a method that can be used to diagnose CAA in chicks, more sensitive, economical and less laborious diagnostic assays are needed.
 ...
PMID:Diagnoses of infections by the so-called chick anemia agent: anemia and direct transmission electron microscopic detection of virus. 178 17

We have identified a common nonpathological polymorphism of the human tyrosinase gene. In Caucasians codon 402 can be either CGA (arginine) [p = .85] or CAA (glutamine) [p = .15]. This polymorphism also occurs in American Blacks, but the codon 402CAA (Gln) allele was not detected in Oriental populations. The substitution of glutamine for arginine at codon 402 results in moderate thermoinstability of the corresponding tyrosinase polypeptide. Tyrosinase enzymatic activity expressed in HeLa cells transfected with a codon 402Gln tyrosinase cDNA is reduced by approximately 75 percent when cells are cultured at 37 degrees C as compared to 31 degrees C, whereas enzymatic activity of codon 402Arg tyrosinase is not temperature-sensitive. However, the genotype at codon 402 of tryosinase is not correlated with the apparent pigmentation phenotype in normal Caucasians.
 ...
PMID:A polymorphism of the human tyrosinase gene is associated with temperature-sensitive enzymatic activity. 182 Feb 7

The nuclear gene atp1 encoding the mitochondrial ATP synthase alpha subunit of the fission yeast Schizosaccharomyces pombe was sequenced. It contains a 1,608-base pair-long open reading frame interrupted by two introns of 175 and 269 base pairs, located near the 5'-end of the gene. The initiation site of transcription AAAC was located 60 nucleotides upstream of the translation initiation codon. The deduced polypeptide sequence contains a 27-amino acid residue presequence, presumably involved in mitochondrial targeting, preceding a mature protein of 509 amino acid residues. The atp1 alleles from mutant A2313 (Bouty, M., and Goffeau, A. (1982) Eur. J. Biochem. 125, 471-477) and its related phenotypic revertant R351 (Falson, P., Di Pietro, A., Darbouret, D., Jault, J. M., Gautheron, D. C., Boutry, M., and Goffeau, A. (1987) Biochem. Biophys. Res. Commun. 148, 1182-1188) were also cloned and sequenced. A single nonsense mutation CAA-TAA (Gln173-stop) in mutant A2313 became a missense mutation TAA-TTA (stop-Leucine) in revertant R351. Glutamine 173 is located in the first putative element of the nucleotide binding site. Its substitution by a leucine residue appears responsible for the lower enzyme affinity toward ADP and for the loss of cooperativity of F1-ATPase activity.
 ...
PMID:Alpha subunit of mitochondrial F1-ATPase from the fission yeast. Deduced sequence of the wild type and identification of a mutation that alters apparent negative cooperativity. 182 97

Twelve-day-old broiler-type chickens had hemorrhagic necrotic wing tips. After 10 blind subcultures in an MDCC-MSB1 cell line, a virus (so-called chick anemia agent [CAA]) was isolated and designated CL-1 CAA. Five-day-old specific-pathogen-free chicken embryos from a commercial breeder flock that were found not to possess antibody against CAA were infected with CL-1 virus via yolk-sac injection. Many (49%) infected embryos were small and apparently had died from severe systemic hemorrhage. Hatched chicks were small and had pale feathers, skin, skeletal muscles, bone marrow, and viscera. All infected chicks had small thymuses. These thymuses often were so small that they could not be found grossly (P = 0.002). Anemia occurred within 4 days post-hatch. Microscopically, all hematopoietic organs were markedly atrophic. Septic necrotizing lesions were seen only in organs from CL-1-injected chicks. Physicochemical and pathological characteristics of this virus indicate that it is similar to other isolates of CAA found in Europe and Japan.
 ...
PMID:Pathogenicity of CL-1 chicken anemia agent. 183 75

Sequencing of sorghum mitochondrial atp6 cDNA clones revealed 19 C-to-U transcript editing events within a 756 bp-conserved core gene; three were silent and 16 resulted in 15 amino acid changes. Only one edit, which was silent, was found in the 381 bp amino-extension to the core gene. Eleven of the 15 changed amino acids were identical with or else represented conservative changes compared to yeast atp6. Editing of a CAA codon to TAA truncates the carboxy-terminus to a position identical to that of yeast. The frequency of editing at sites which change amino acids was very high in contrast to partial editing at silent, third base, sites.
 ...
PMID:RNA editing of sorghum mitochondrial atp6 transcripts changes 15 amino acids and generates a carboxy-terminus identical to yeast. 183 73

A 203-base-pair sequence 5' of the latency-associated transcripts (LATs) of herpes simplex virus type 1 contains a 7-base consensus sequence TGCGTCA that is identical to the cAMP-response element of the proenkephalin gene. This consensus sequence is at -38 relative to the putative 5' end of the LATs with a TATA box at the -24 position. In transient chloramphenicol acetyltransferase assays in rat pheochromocytoma (PC12) cells, this enhancer region stimulated gene expression up to 3-fold in the presence of dibutyryl cAMP, forskolin, nerve growth factor, or phorbol 12-myristate 13-acetate. Mutation of the cAMP-response element to TGCG-CAA resulted in a 4-fold reduction of basal activity and a complete loss of inducible stimulation. In DNA gel retardation assays, purified cAMP-response element-binding protein and a nuclear protein from PC12 cells were shown to bind specifically to this element. Furthermore, it was demonstrated that the reactivation of wild-type herpes simplex virus type 1 from dissociated latently infected murine trigeminal ganglia was significantly accelerated (P less than 0.005) by the addition of cAMP analogs or adenylate cyclase activators. However, these reagents did not accelerate reactivation of a deletion mutant that lacks the putative cAMP-response element-containing promoter region, transcriptional start site, and 1015 base pairs of the LATs. These studies demonstrate that the promoter region of the LATs contains a functional cAMP-response element and that expression of the LATs is likely controlled by second messenger signal transduction and imply a role for cAMP in triggering viral reactivation.
 ...
PMID:The promoter of the latency-associated transcripts of herpes simplex virus type 1 contains a functional cAMP-response element: role of the latency-associated transcripts and cAMP in reactivation of viral latency. 184 42


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>