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)

We have analyzed the expression of the CDKN1A (p21(CIP1)), CDKN1B (p27(Kip1)), TP53, RB1 and MDM2 proteins and tumor cell proliferation by immunohistochemical staining in 59 cases of metastatic melanoma. The genomic status of the CDKN2A (INK4-ARF, p16/p14(ARF)), CDKN2B (p15) and CDKN2C (p18) genes was determined by PCR-SSCP (single-strand conformation polymorphism) in 46 of these cases. These results were correlated with various clinico-pathological parameters, including the outcome of combined chemoimmunotherapy. We found positive correlations between the expression of CDKN1A and MDM2 (r = 0.5063, P = 0.001), between the expression of CDKN1B and RB1 (r = 0.5026, P = 0.001), and between RB1 expression and tumor cell proliferation (0.5564, P<0.001). Two mutations in the CDKN2A (p16) gene were detected, including a novel base change AAC-->ATC (Asn to Ile) at codon 71, that also changes the codon 85 of the alternative reading frame gene p14(ARF) from CAA to CAT (Gln to His). Homozygous deletion at exon 2 of the CDKN2A (INK4-ARF) gene was detected in six cases. In seven cases, the 540C-->G polymorphism in the 3'UTR of the CDKN2A (p16) gene was found in linkage disequilibrium with the 74C-->A polymorphism in intron 1 of the CDKN2B gene (P < 0.0001). These cases had significantly lower expression of the TP53 protein (P = 0.0032). Both 540C-->G and 580C-->T polymorphisms in the 3'UTR of the CDKN2A (p16) gene were associated with significantly shorter progression time from primary to metastatic disease (P = 0.0071). We conclude, that although none of the analyzed cell cycle regulators could be singled out as a major prognostic factor, G(1)/S checkpoint abnormalities remain one of the most significant factors in the development of malignant melanoma.
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PMID:Analysis of G(1)/S checkpoint regulators in metastatic melanoma. 1086 49

The 5'-leader sequence (called Omega) of tobacco mosaic virus (TMV) functions as a translational enhancer in plants. A poly(CAA) region within Omega is responsible for the translation enhancement and serves as a binding site for the heat shock protein, HSP101, which is required for the translational enhancement. Genetic analysis of the HSP101-mediated enhancement of translation from Omega-containing mRNA suggested that two eukaryotic initiation factors (eIFs), i.e. eIF4G and eIF3, were necessary. In this study, the functional interaction between Omega and other RNA elements known to participate in the recruitment of eIF4G, i.e. the 5'-cap and the poly(A) tail, was examined. Omega exhibited functional overlap with the 5'-cap and the poly(A) tail but not with the native TMV 3'-UTR which contains an independent translational enhancer. Consistent with the role of HSP101 in mediating the translational function of Omega, the enhancement afforded by Omega increased following a heat shock, which elevates expression of HSP101. The use of a fractionated translation lysate revealed that of the two eIF4F proteins present in plants, eIF4F was specifically required for the activity of Omega. The data suggest that Omega is functionally similar to a 5'-cap and a poly(A) tail in that it serves to recruit eIF4F in order to enhance translation from an mRNA.
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PMID:The 5'-leader of tobacco mosaic virus promotes translation through enhanced recruitment of eIF4F. 1214 Mar 25

Full-length cDNA of a mannose-binding lectin or agglutinin gene was cloned from a traditional Chinese medicinal herb Crinum asiaticum var. sinicum through RACE-PCR cloning. The full-length cDNA of C. asiaticum agglutinin (caa) was 820 bp and contained a 528 bp open reading frame encoding a lectin precursor (preproprotein) of 175 amino acid residues with a 22 aa signal peptide. The coding region of the caa gene was high in G/C content. The first 20 bp of the 5' UTR had a dC content of 50%, which was a typical feature of the leader sequence. By cutting away the signal peptide, the CAA proprotein was 15.79 kDa with a pl of 9.27 and contained 3 mannose-binding sites (QDNY). Random coil and extended strand constituted interlaced domination of the main part of the secondary structure. B-lectin conserved domain existed within N24 to G130. Predicted three-dimensional structure of CAA proprotein was very similar to that of GNA (Galanthus nivalis agglutinin). It is significant that besides certain homologies to known monocot mannose-binding lectins from Amaryllidaceae, Orchidaceae, Alliaceae and Liliaceae, caa also showed high similarity to gastrodianin type antifungal proteins. No intron was detected within the region of genomic sequence corresponding to the caa full-length cDNA. Southern blot analysis indicated that the caa gene belonged to a low-copy gene family. Northern blot analysis demonstrated that caa mRNA was constitutively expressed in all the tested tissue types including the root, bulb, leaf, rachise, flower and fruit tissues.
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PMID:Molecular cloning and characterization of a mannose-binding lectin gene from Crinum asiaticum. 1296 67

The degree of interpatient variability in the warfarin dose required to achieve the desired anticoagulant response can only partly be explained by polymorphisms in the CYP2C9 gene, suggesting that additional genetic factors such as polymorphisms in genes involved in blood coagulation may influence warfarin dose requirement. In total, 165 Caucasian outpatients on stable maintenance warfarin treatment previously genotyped for CYP2C9 were analysed for common polymorphisms in FVII, GGCX and VKORC1 genes. The -402G > A polymorphism and a variable number of repeats in intron 7 of FVII gene did not significantly influence warfarin dose. The mean warfarin doses increased with the number of (CAA) repeats in the GGCX gene, but the differences were significant only in the CYP2C9*1/*1 subgroup of patients (p = 0.032). Common polymorphism (6484C > T) in intron 1 of the VKORC1 gene led to lower warfarin dose requirement; the means were 5.70 (95% C.I. 4.95-6.45), 3.49 (3.07-3.90) and 2.11 (1.80-2.42) mg/day for 6484 CC, CT and TT genotypes, respectively (p < 0.001). In contrast, 9041G > A polymorphism in 3'UTR of theVKORC1 gene led to higher warfarin dose requirement; the means were 3.09 (2.58- 3.60), 4.26 (3.69-4.82) and 5.86 (4.53-7.19) mg/day for 9041 GG, GA and AA genotypes, respectively (p < 0.001). With a regression model we explained 60.0% of variability in warfarin dose, which was due to gene polymorphisms (CYP2C9, VKORC1), age and body-surface-area. When aiming for individualised warfarin therapy, at least VKORC1 polymorphisms should be included in predictive genotyping besides CYP2C9.
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PMID:The influence of sequence variations in factor VII, gamma-glutamyl carboxylase and vitamin K epoxide reductase complex genes on warfarin dose requirement. 1667 68

To improve expression levels of recombinant proteins in plants, a new leader sequence was designed. Several elements known to enhance gene translation and/or transcription were considered, including the CaMV 35S Inr site, a CT-rich motif often shared by highly expressed plant genes and a poly(CAA) region widespread in tobamovirus and plant leaders. The effect of the synthetic leader on gusA expression was evaluated in genetically modified tobacco plants by measuring the beta-glucuronidase activity and the mRNA level. When compared to the gusA leader of pBI121, the new sequence determined a 8.6-fold and a 12.5-fold increase of enzyme concentration taking into account the whole plant population or the above-average expressors, respectively. Since most pCAMBIA vectors harbour a very short 5'-UTR, identical to a fragment of the pBI121 leader, leader replacement with the sequence herein described is strongly suggested.
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PMID:Improvement of the pBI121 plant expression vector by leader replacement with a sequence combining a poly(CAA) and a CT motif. 1723 82

The 5'-untranslated region (5'-UTR) of RNA of tobacco mosaic virus (TMV), called omega sequence, is known as an mRNA leader promoting efficient initiation of translation. The central part of the sequence consists of many CAA repeats, which were reported to be mainly responsible for the enhancing activity of the omega leader. In this work we synthesized the polyribonucleotides containing either the natural omega sequence or the regular (CAA)(n) sequence, and studied them using UV spectrophotometry and analytical ultracentrifugation methods. It was demonstrated that the polyribonucleotides manifest significant hypochromicity, cooperative melting of their structures upon heating, high melting temperature, and the sedimentation coefficients typical of compactly folded RNAs of this size. Thus, the omega leader and its core (CAA)(n) repeat sequence devoid of secondary structure of the Watson-Crick type seem to be well structured elements of mRNA.
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PMID:The leader sequence of tobacco mosaic virus RNA devoid of Watson-Crick secondary structure possesses a cooperatively melted, compact conformation. 1748 61

Congenital heart disease is the most common type of birth defect and the leading cause of infant mortality in the first year of life. Ventricular septal defect (VSD) is one of the most general congenital heart defects and is a defect in the wall between the right and left ventricles of the heart. The pathogenesis of VSD has been extensively investigated for many years, but it remains uncertain. To determine whether reticulon 4 gene (RTN4) 3'UTR insertion/deletion polymorphisms are associated with VSD, we genotyped the TATC and CAA insertion/deletion polymorphisms of RTN4 by polymerase chain reaction-polyacrylamide gel electrophoresis in 151 VSD patients and 308 unrelated healthy subjects in a Chinese Han population. No significant differences in 3'UTR TATC and CAA insertion/deletion polymorphisms genotype and allele frequencies were observed between the VSD and controls. These data indicate that, for the first time, RTN4 3'UTR insertion/deletion polymorphisms may not appear to play a role in the susceptibility of VSD in Chinese Han population.
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PMID:Analysis of RTN4 3'UTR insertion/deletion polymorphisms in ventricular septal defect in a Chinese Han population. 2116 2

Recent studies have suggested that RTN4 is a multifunctional gene, including inhibition of axonal regeneration, vascular remodeling, apoptosis, and tumor suppression. The TATC and CAA insertion/deletion polymorphisms of RTN4 3'-UTR have been linked to schizophrenia, depression, and dilated cardiomyopathy. To test whether these two polymorphisms are associated with cervical squamous cell carcinoma (CSCC), in this research, by using polymerase chain reaction-polyacrylamide gel electrophoresis, we determined the genotypes of the TATC and CAA polymorphisms in 336 CSCC patients and 450 unrelated control subjects. Allele frequencies of TATC and CAA polymorphisms were not significantly different between CSCC patients and control subjects (odds ratio [OR]=1.22, 95% confidence interval [CI]=0.98-1.50 for TATC; OR=0.95, 95% CI=0.76-1.18 for CAA). Decreased CSCC risk was associated with TATC polymorphism in a recessive model (OR=0.49, 95% CI=0.30-0.77), while no significant association was observed between CAA polymorphism and CSCC in different genetic models. Results of stratified analysis revealed that both TATC and CAA polymorphisms were associated with high clinical stage, and CAA polymorphism was also associated with positive parametrial invasion (OR=0.69, 95% CI=0.48-0.98). The present study provides evidence that TATC and CAA insertion/deletion polymorphisms are associated with CSCC, indicating that genetic variation in RTN4 3'-UTR contributes to the susceptibility to CSCC. It is necessary to confirm these findings in ethnically different populations and with a larger sample.
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PMID:Genetic variation in RTN4 3'-UTR and susceptibility to cervical squamous cell carcinoma. 2232 Aug 44

This pilot case-control study was conducted to test the hypothesis that the TATC (rs71682890) and CAA (rs34917480) insertion/deletion polymorphisms of RTN4 3'-UTR are associated with the susceptibility to uterine leiomyoma (UL). The study recruited 286 premenopausal women with UL and 450 unrelated postmenopausal women not presenting the disease as control subjects. The polymorphisms of rs71682890 and rs34917480 were genotyped with the method of polymerase chain reaction polyacrylamide gel electrophoresis (PCR - PAGE). No statistically significant association was observed between the TATC insertion/deletion polymorphism and UL risk. However, increased UL risk was identified to be significantly associated with CAA insertion/deletion polymorphism in the recessive and codominant model. The present study provided evidence for the first time that CAA polymorphism in RTN4 3'-UTR, but not TATC polymorphism may be involved in susceptibility to UL.
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PMID:Association of genetic variations in RTN4 3'-UTR with risk of uterine leiomyomas. 2347 81

Nogo protein, encoded by gene reticulon-4 (RTN4), includes three major isoforms by different splicing, named Nogo-A Nogo-B and Nogo-C. Nogo proteins play an important role in the apoptosis of cells, especially in tumor cells. RTN4 single nucleotide polymorphisms (SNPs) can influence the efficiency of transcription and translation thus being related with an individual's predisposition to cancer. The CAA insertion/deletion polymorphism (rs34917480) within RTN4 3'-UTR has been reported to be associated with many cancer types. In order to investigate the relationship between this polymorphism and susceptibility to non-small cell lung cancer (NSCLC) in the Chinese population, we conducted the present case-control study including 411 NSCLC patients and 471 unrelated healthy controls. The genotype distributions were significantly different between cases and controls (p=0.014). We found that the del allele could significantly increase NSCLC risk (ins/ins vs ins/del: p=0.007, OR 1.46, 95%CI=1.11-1.93; dominant model: p=0.004, OR 1.47, 95%CI=1.13-1.92 and allele model: p=0.008, OR 1.35, 95%CI=1.08-1.67). This association was stronger in participants over 60 years old, males and smokers. We therefore conclude that the CAA insertion/deletion polymorphism (rs34917480) contributes to non-small cell lung cancer risk in Chinese population. Age, sex and environmental exposure are also related to carcinogenic effects of rs34917480.
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PMID:RTN4 3'-UTR insertion/deletion polymorphism and susceptibility to non-small cell lung cancer in Chinese Han population. 2504 Sep 83


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