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

Human livers produce apoB-100, a major protein of VLDL, while intestines produce apoB-48, the major protein of chylomicrons. ApoB-48 is translated from apoB-100 mRNAs that are post-transcriptionally edited at codon 2153, converting CAA (glutamine) to TAA, a stop codon. In contrast to humans, mouse and rat livers contain the apoB-100 mRNA editing mechanism. Because hormones and nutrients affect the metabolism of apoB containing lipoproteins, we studied the effects of sex hormones and diets on apoB mRNA editing. Groups of male and female C3H/HeJ mice were castrated and treated with 17 beta-estradiol at 0.16 (E2L) or at 5 micrograms (E2H), or with testosterone propionate at 1 microgram/g body weight/day for 14 days. Plasma apoB levels and ratios of apoB-100/apoB-48 both increased 2-fold, but only in the E2H group. To determine if the increased apoB-100/apoB-48 ratios were associated with altered levels of apoB-100 and apoB-48 mRNA, both forms of apoB mRNA were quantified. We found that indeed ApoB-100 mRNA increased 1.8-fold (p < 0.025) compared to apoB-48 mRNA only in the E2H group. Next, we studied the individual effects of dietary fatty acids and dietary cholesterol on the relative abundance of apoB-100 and apoB-48 mRNA. Contrary to the estrogen effect, the high fat-combination diet increased apoB-48 mRNA relative to apoB-100 mRNA. Total plasma apoB as well as apoB-48 synthesis in liver also increased. Our studies demonstrate that estrogens and high fat diet both modulate apoB editing in mouse liver, but that estrogens and fat diet affected apoB mRNA editing in opposite directions.
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PMID:Hormonal and nutritional stimuli modulate apolipoprotein B mRNA editing in mouse liver. 141 37

We have examined the effects of prolonged histidine deprivation on the reversion of Salmonella typhimurium histidine auxotrophs containing either hisG46, a missense mutation (CTC----CCC), or hisG428, an ochre mutation (CAA----TAA). Both of these mutants can revert to His+ via intragenic and extragenic mechanisms. Whereas the hisG46 mutant site consists of G/C base pairs, extragenic suppression of hisG46 requires mutation at an A/T site. Conversely, the hisG428 site itself contains only A/T base pairs, and extragenic suppression of hisG428 occurs principally at G/C sites. Thus, by examining the mutational spectrum of hisG46 and hisG428 revertants that occurred in the presence and in the absence of histidine, it was possible to determine the effects of histidine starvation on mutations at G/C vs. A/T sites as well as on intragenic sites vs. extragenic suppressor sites. Using DNA-colony hybridization, we determined the DNA sequences of over 1300 hisG46 and hisG428 revertants. Histidine-independent revertants that arose during growth in liquid medium that contained histidine included both intragenic and extragenic suppressor mutations. The relative frequency of such extragenic suppressors was greatly reduced among the His+ revertants that were isolated after 5-10 days of histidine starvation on agar medium. Moreover, DNA sequence analysis revealed striking differences in the distribution of particular transversions at the hisG428 locus in revertants arising after prolonged histidine starvation as compared to those arising after growth in the presence of histidine.
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PMID:Sequence analysis of mutations arising during prolonged starvation of Salmonella typhimurium. 142 30

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.
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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

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.
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PMID:RNA editing of sorghum mitochondrial atp6 transcripts changes 15 amino acids and generates a carboxy-terminus identical to yeast. 183 73

Human apolipoprotein (apo) B exists in plasma as two isoproteins designated apoB-100 and apoB-48. ApoB-100 (512 kDa) and apoB-48 (250 kDa) are synthesized by the liver and intestine respectively. Analysis of apoB cDNA clones isolated from a human intestinal cDNA library revealed that the intestinal apoB mRNA contains a new in-frame translational stop codon. This premature stop codon is generated by a single base substitution of a 'C' to 'T' at nucleotide 6538 which converts the codon 'CAA' coding for the amino acid glutamine residue 2153 to an in-frame stop codon 'TAA'. The generation of a stop codon in the intestinal apoB mRNA appears to be tissue specific since it has not been reported in cDNA clones isolated from human liver cDNA libraries which code for the 4536 amino acid apoB-100. A potential polyadenylation signal sequence 'AATAAA' was also identified 390 bases downstream from the new stop codon. The new stop codon in the human intestinal apoB mRNA provides a potential mechanism for the biosynthesis of intestinal apoB-48.
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PMID:Identification of a novel in-frame translational stop codon in human intestine apoB mRNA. 244 42

Apolipoprotein (apo) B occurs in two forms, apoB100 (512 kDa) and apoB48 (240 kDa); both are derived from the same gene. A novel mechanism involving editing of the apoB mRNA causes the formation of apoB48; the first base of codon 2153 is changed from cytosine to uracil, converting a glutamine codon to a premature stop codon. To identify the apoB mRNA sequence elements recognized by the apoB mRNA editing mechanism, two apoB cDNA fragments (354 and 63 base pairs) with codon 2153 near their centers were inserted into a high expression vector of another secreted apolipoprotein, apoE. The resulting vectors, pHEB-354 and -63, were transfected into Chinese hamster ovary cells, HepG2 cells, and apoB48-producing CaCo-2 cells. The secreted chimeric apolipoproteins (apoEB354 and apoEB63) were analyzed for premature truncation, and the mRNA was analyzed for the presence of an edited base. The pHEB-354 construct produced a truncated protein only in CaCo-2 cells, whereas pHEB-63 produced no truncated protein in any of the three cell types. The mRNA was converted to cDNA and amplified by the polymerase chain reaction technique. Differential hybridization of the polymerase chain reaction products with CAA (Gln) and TAA (Stop) specific probes detected an edited base only in cDNA from CaCo-2 cells transfected with pHEB-354, in agreement with the protein analysis. We conclude that the nucleotide sequence of the apoB cDNA insert in pHEB-354 contains sufficient information to be edited in CaCo-2 cells. In these cells, a cryptic polyadenylation site was activated in the edited pHEB-354 mRNA. As a result, CaCo-2 cells transfected with pHEB-354 produced a short, edited pHEB-354 mRNA and a long, unedited pHEB-354 mRNA. Chinese hamster ovary cells transfected with pHEB-354 or CaCo-2 cells transfected with pHEB-63 produced only a full length transcript. Amplification of the pHEB-354 cDNA using 3'-primers upstream and downstream of the poly(A) addition site and hybridization with the TAA probe confirmed these results. This unusual mRNA editing apparently occurs before polyadenylation, probably in the nucleus.
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PMID:Apolipoprotein B48 RNA editing in chimeric apolipoprotein EB mRNA. 247 6

The gene-sized macronuclear DNA of the hypotrichous ciliate Stylonychia lemnae contains one size class of DNA molecules of 1.85 kb (1 kb = 10(3) base-pairs) coding for beta-tubulin. These DNA molecules consist of two different beta-tubulin genes, beta 1 and beta 2, which are amplified to about 150,000 (beta 1) and 30,000 (beta 2) copies per macronucleus. Both genes were cloned and sequenced entirely. The coding sequences of the two molecules (1329 base-pairs including TGA) predict identical amino acid sequences for the proteins and show a nucleotide homology of 97.2%. The nucleotide as well as the encoded amino acid sequences are highly conserved, when compared to beta-tubulin genes from vertebrates. The ciliate-specific codon TAA specifying glutamine is present only in the beta 2-tubulin gene, whereas glutamine is encoded soley by CAA in the beta 1-tubulin gene. The 5' and 3'-non-coding regions of both beta-tubulin genes are similar in length, but differ extremely in nucleotide sequence. Both beta-tubulin genes are transcriptionally active in S. lemnae, although not all putative transcription-regulatory sequences known from higher eukaryotes can be detected within the non-coding regions. The two transcription products localized by S1-mapping experiments show a similar length of about 1.40 kb and transcription seems to be regulated differently for beta 1 and beta 2.
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PMID:Nucleotide sequence and expression of two beta-tubulin genes in Stylonychia lemnae. 312 2

A Batak Indonesian from North Sumatra with hemoglobin (Hb) D Punjab (alpha 2 beta 2 121----Gln) and hemoglobin Constant Spring (Hb CoSp) is described. The 24-year-old man did not have clinical symptoms, and his hematological indices were normal. However, he had a persistent slight elevation of fetal hemoglobin level. His mother and his brother were heterozygous for Hb D Punjab; his father had Hb CoSp trait. A sister did not have any abnormal hemoglobin. To show the exact molecular defect leading to the synthesis of Hb CoSp in this family, genomic DNA from the father was analyzed by hybridization with synthetic oligonucleotides. Genomic DNA was digested with Sst I and Hind III producing a 1.05-kb fragment from the 3' end segment of the alpha 2-globin gene, including the termination codon. Two nonadecamers were synthesized to serve as probes: one, entirely homologous to the normal 3' end of alpha 2A-globin gene sequence, including the termination codon TAA, the other different from it by a replacement of the T in the termination codon TAA with C, changing it to CAA, the codon for the amino acid glutamine. DNA from normal controls gave a positive signal with the normal alpha 2TAA oligonucleotide probe but negative with the alpha 2 CAA probe. The father of propositus who had Hb CoSp trait gave a positive signal with the normal alpha 2TAA oligonucleotide probe as well as with the alpha 2CAA oligonucleotide probe, showing him to be heterozygous for the alpha 2CAA-globin gene. This result shows that the Hb CoSp in the Batak family is indeed due to a replacement of T by C in the TAA termination codon of the alpha 2-globin gene changing it to CAA the condon for glutamine. This explains the resulting readthrough of the untranslated sequence of the mRNA.
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PMID:Hemoglobin constant spring defined by specific oligonucleotide hybridization and hemoglobin D Punjab (beta 121----Gln) in a Batak Indonesian family. 317 65

Apolipoprotein B (apoB) biosynthesis by rat liver was studied following thyroid hormone (3,5,3'-triiodo-L-thyronine) administration to hypothyroid rats. Pharmacologic doses of 3,5,3'-triiodo-L-thyronine caused suppression of apoB100 synthesis but did not affect apoB48 levels. There was no detectable apoB100 synthesis in hyperthyroid rats. To examine whether these results were mediated by the previously demonstrated mechanism of RNA modification (Powell, L. M., Wallis, S. C., Pease, R. J., Edwards, Y. H., Knott, T. J., and Scott, J. (1987) Cell 50, 831-840), the DNA sequence corresponding to the C-terminal end of rat apoB48 was determined from rat liver cDNA clones. Rat cDNAs contained a stop codon at an identical position to that found in human and rabbit apoB48 intestinal cDNA. To quantitate the relative amounts of apoB100 and apoB48 message, cDNA was synthesized from hepatic and intestinal apoB RNA and a 207-base pair fragment amplified using the polymerase chain reaction. The products were then differentially hybridized with oligonucleotides specific for apoB100 (containing CAA) or apoB48 (TAA). Control and hypothyroid liver contained approximately equal amounts of CAA and TAA, while hyperthyroid liver contained greater than 90% TAA. All gut samples contained 94-98% TAA. Genomic DNA from rat liver contained only CAA. The results demonstrate that apoB mRNA modification can be hormonally modulated in the adult rat by induction of a mechanism involving substitution of a stop codon into hepatic apoB100 mRNA.
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PMID:Thyroid hormone modulates the introduction of a stop codon in rat liver apolipoprotein B messenger RNA. 341 67

Genetic analysis of histidine independent (His+) revertants induced by ultraviolet light in the his-4 E. coli strain AB1157 was carried out: 93% carried ochre (UAA) suppressor mutations and 17% carried back mutations to his+ or (intragenic?) suppressors not detectably separable from his-4. Using the specialized transducing lambda psu 2int- phage, which carries supE-supB, it was determined that 87% of the ochre suppressors mapped in the supE-supB region. We were able to deduce that 56% of these affected tRNA1Gln by a CAA leads to TAA change in the tRNA gene while 31% affected tRNA2Gln by TAG- leads to TAA change. Although we were unable to deduce the base substitution of the remaining 13%, the results indicate that most of the suppressor mutations are caused by G:C to A:T transition. These results suggest that the high incidence of supE-supB region suppressor mutation in E. coli by UV would be a reflection of the general feature of UV mutagenesis; i.e. preferential induction of G:C to A:T transition in repairing nonpairing DNA lesions. AI 05371
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PMID:Analysis of ultraviolet light-induced suppressor mutations in the strain of Escherichia coli K-12 AB1157: an implication for molecular mechanisms of UV mutagenesis. 645 Aug 70


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