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

The evolutionary history of human chromosome 20 in primates was investigated using a panel of human BAC/PAC probes spaced along the chromosome. Oligonucleotide primers derived from the sequence of each human clone were used to screen horse, cat, pig, and black lemur BAC libraries to assemble, for each species, a panel of probes mapping to chromosomal loci orthologous to the loci encompassed by the human BACs. This approach facilitated marker-order comparison aimed at defining marker arrangement in primate ancestor. To this goal, we also took advantage of the mouse and rat draft sequences. The almost perfect colinearity of chromosome 20 sequence in humans and mouse could be interpreted as evidence that their form was ancestral to primates. Contrary to this view, we found that horse, macaque, and two New World monkeys share the same marker-order arrangement from which the human and mouse forms can be derived, assuming similar but distinct inversions that fully account for the small difference in marker arrangement between humans and mouse. The evolutionary history of this chromosome unveiled also two centromere repositioning events in New World monkey species.
Mol Biol Evol 2005 Feb
PMID:Evolutionary history of chromosome 20. 1549 55

Leishmania is a group of protozoan parasites which causes a broad spectrum of diseases resulting in widespread human suffering and death, as well as economic loss from the infection of some domestic animals and wildlife. To further understand the fundamental genomic architecture of this parasite, and to accelerate the on-going sequencing project, a whole-genome XbaI restriction map was constructed using the optical mapping system. This map supplemented traditional physical maps that were generated by fingerprinting and hybridization of cosmid and P1 clone libraries. Thirty-six optical map contigs were constructed for the corresponding known 36 chromosomes of the Leishmania major Friedlin genome. The chromosome sizes ranged from 326.9 to 2821.3 kb, with a total genome size of 34.7 Mb; the average XbaI restriction fragment was 25.3 kb, and ranged from 15.7 to 77.8 kb on a per chromosomes basis. Comparison between the optical maps and the in silico maps of sequence drawn from completed, nearly finished, or large sequence contigs showed that optical maps served several useful functions within the path to create finished sequence by: guiding aspects of the sequence assembly, identifying misassemblies, detection of cosmid or PAC clones misplacements to chromosomes, and validation of sequence stemming from varying degrees of finishing. Our results also showed the potential use of optical maps as a means to detect and characterize map segmental duplication within genomes.
Mol Biochem Parasitol 2004 Nov
PMID:Shotgun optical mapping of the entire Leishmania major Friedlin genome. 1550 Sep 21

Allele-specific competitive blocker PCR (ACB-PCR) amplification and quantification was developed for mouse p53 codon 270 CGT-->TGT base substitution and codon 244/245 AAC/CGC-->AAT/TGC tandem mutation. PCR products corresponding to p53 mutant and wild-type DNA sequences were generated. These DNAs were mixed in known proportions to construct samples with defined mutant fractions and the allele-specific detection of each mutation was systematically optimized. Each assay was used to analyze eight simulated solar light (SSL)-induced tumors. By analyzing mutant fraction (MF) standards in parallel with PCR products generated from tumor samples, p53 mutants could be quantified as subpopulations within the tumors. All eight tumors contained detectable levels of p53 codon 270 CGT-->TGT mutation. Three tumors had p53 MFs between 10(-4) and 10(-3). Five tumors had p53 MFs between 10(-3) and 10(-2). None of the eight mouse skin tumors had measurable levels of p53 codon 244/245 tandem mutation. Frequent detection of p53 codon 270 CGT-->TGT mutation provides additional evidence that a pyrimidine dinucleotide overlapping a methylated CpG site (Pyr(me)CG) is a susceptible target for SSL-induced mutagenesis. The absence of p53 codon 244/245 mutation in tumors may be explained by its mutant p53 phenotype and/or indicate that this site is not methylated. These initial results indicate that p53 codon 270 CGT-->TGT mutation may be a sensitive biomarker for SSL- or UV-induced mutagenesis. This mutational endpoint may be useful for evaluating the co-carcinogenicity of compounds administered in combination with UV or SSL.
Environ Mol Mutagen 2005 Jun
PMID:Quantifying levels of p53 mutation in mouse skin tumors. 1566 16

Over the last decade transgenic mouse models have become a common experimental tool for unraveling gene function. During this time there has been a growing expectation that transgenes resemble the in vivo state as much as possible. To this end, a preference away from heterologous promoters has emerged, and transgene constructs often utilize the endogenous promoter and gene sequences in BAC, PAC and YAC form without the addition of selectable markers, or at least their subsequent removal. There has been a trend toward controlled integration by homologous recombination, either at a characterized chromosomal localization or in some cases within the allele of interest. Markers such as green fluorescent protein (GFP), beta-galactosidase (LacZ), and alkaline phosphatase (AP) continue to be useful to trace transgenic cells, or transgene expression. The development of technologies such as RNA interference (RNAi), are introducing new ways of using transgenic models. Future developments in RNAi technology may revolutionize tissue specific inactivation of gene function, without the requirement of generating conditionally targeted mice and tissue specific recombinase mice. Transgenic models are biological tools that aid discovery. Overall, the main consideration in the generation of transgenic models is that they are bona fide biological models that best impart the disease model or biological function of the gene that they represent. The main consideration is to make the best model for the biological question at heart and this review aims to simplify that task somewhat. Here we take a historical perspective on the development of transgenic models, with many of the important considerations to be made in design and development along the way.
Mol Biotechnol 2005 Feb
PMID:Making better transgenic models: conditional, temporal, and spatial approaches. 1569 70

To understand the role of growth hormone-releasing hormone (GHRH) and pituitary adenylate cyclase-activating polypeptide (PACAP) and to examine the functional significance of the co-expression of GHRH and PACAP in fish, their receptors were characterized in zebrafish. Three cDNAs encoding the PAC(1) receptor, the VPAC(1) receptor, and the partial GHRH receptor were identified from zebrafish. Functional expression of the PAC(1) and VPAC(1) receptors revealed that both are potently coupled to the adenylyl cyclase pathway, but only the PAC(1) receptor is coupled to the phospholipase C pathway. Transcripts for all three receptors were widely distributed, often in an overlapping pattern in the adult zebrafish. Also, one splice variant of the partial GHRH receptor and three splice variants of the PAC(1) receptor were identified from adult zebrafish. The long GHRH receptor transcript contained a 27 amino acid insert in transmembrane domain 5 encoding a premature stop codon leading to a truncated receptor protein. For the PAC(1) receptor, two of the splice variants corresponded to the hop1 and hop2 variants characterized in mammals. The third splice variant identified from the gill encoded a novel 107 bp insert containing a premature stop codon. Therefore, PACAP and GHRH have widespread, overlapping target sites suggesting a coordinated role for these hormones in evolution.
Mol Cell Endocrinol 2005 Feb 28
PMID:Characterization of four receptor cDNAs: PAC1, VPAC1, a novel PAC1 and a partial GHRH in zebrafish. 1571 35

In contrast to previous steady-state analyses of the O(2)-responsive transcriptome, here we examined the dynamics of the response to short-term anaerobiosis (2 generations) in both catabolite-repressed (glucose) and derepressed (galactose) cells, assessed the specific role that Msn2 and Msn4 play in mediating the response, and identified gene networks using a novel clustering approach. Upon shifting cells to anaerobic conditions in galactose medium, there was an acute ( approximately 10 min) yet transient (<45 min) induction of Msn2- and/or Msn4-regulated genes associated with the remodeling of reserve energy and catabolic pathways during the switch from mixed respiro-fermentative to strictly fermentative growth. Concomitantly, MCB- and SCB-regulated networks associated with the G(1)/S transition of the cell cycle were transiently down-regulated along with rRNA processing genes containing PAC and RRPE motifs. Remarkably, none of these gene networks were differentially expressed when cells were shifted in glucose, suggesting that a metabolically derived signal arising from the abrupt cessation of respiration, rather than O(2) deprivation per se, elicits this "stress response." By approximately 0.2 generation of anaerobiosis in both media, more chronic, heme-dependent effects were observed, including the down-regulation of Hap1-regulated networks, derepression of Rox1-regulated networks, and activation of Upc2-regulated ones. Changes in these networks result in the functional remodeling of the cell wall, sterol and sphingolipid metabolism, and dissimilatory pathways required for long-term anaerobiosis. Overall, this study reveals that the acute withdrawal of oxygen can invoke a metabolic state-dependent "stress response" but that acclimatization to oxygen deprivation is a relatively slow process involving complex changes primarily in heme-regulated gene networks.
Mol Cell Biol 2005 May
PMID:Dynamical remodeling of the transcriptome during short-term anaerobiosis in Saccharomyces cerevisiae: differential response and role of Msn2 and/or Msn4 and other factors in galactose and glucose media. 1587 Feb 79

Alpha1-antitrypsin deficiency (AATD) is a common hereditary disorder associated with high risk of developing pulmonary emphysema early in life and, to a lesser extent, chronic liver disease and cirrhosis. Among Northern Europeans and Northern Americans, more than 95% of individuals with emphysema associated with AATD carry the most frequent AAT deficient gene variants, PI*Z and PI*S. Rare AAT deficient variants account for 2-4% of AATD individuals. We extend the sequence data on AAT by characterizing a novel Null allele detected in 3 subjects: a carrier belonging to an Italian/Egyptian family and 2 members of a family originating from Southern Italy. The mutation raised on a M1 (Ala213) base allele and it is characterized by an A-->T transversion at exon III, nt 218, codon 259 (AAA-->TAA) (GeneBank accession number AY 256958). The transversion results in a premature stop codon (Lys259AAA-->Stop259TAA). The proposed nomenclature of Q0cairo is from the birthplace of the father of first recognized subject. Serum levels and isoelectric focusing of AAT were consistent with the presence of the Null variant.
Diagn Mol Pathol 2005 Jun
PMID:Identification of a novel alpha1-antitrypsin null variant (Q0Cairo). 1590 97

The ground state geometric, electronic structure and Raman spectra of 5,15-diphenylporphine (H(2)DPP) have been studied using B3LYP/6-31G(d) method and compared with that of well-studied free base porphine (H(2)P) and meso-tetraphenylporphine (H(2)TPP). Calculation shows that 5,15-substitution causes remarkable in-plane distortion, whereas the resulting out-of-plane distortion is negligible. The calculated electronic structure of H(2)DPP is consistent with the absorption spectra compared with H(2)P and H(2)TPP. The calculated vibrational frequencies of H(2)DPP scaled with a single factor of 0.971 agree well with experimental data (the rms error is 8.0 cm(-1)). The assignment of experimental Raman bands of H(2)DPP was discussed on the basis of theoretical calculation and the comparison with that of H(2)P and H(2)TPP. The splitting of some vibrational modes involving the motion of C(m) atom, such as nu(1), nu(8), and nu(10), was observed and was attributed to the diversification of the environment around C(m) atoms. As the shift of absorption peaks, the shift of some structure-sensitive Raman bands of H(2)DPP form that of H(2)TPP and H(2)P was attributed to the in-plane nuclear reorganization (IPNR) induced by phenyl-substitution, though the contribution of nonplanarity mechanism could not be excluded completely.
Spectrochim Acta A Mol Biomol Spectrosc 2005 Nov
PMID:DFT study on the geometric, electronic structure and Raman spectra of 5,15-diphenylporphine. 1625 97

Mutations in the PTPN11 gene, which encodes the protein tyrosine phosphatase SHP-2, causes Noonan syndrome (NS), an autosomal dominant disorder with pleomorphic developmental abnormalities. Certain germline and somatic PTPN11 mutations cause leukemias. Mutations have gain-of-function (GOF) effects with the commonest NS allele, N308D, being weaker than the leukemia-causing mutations. To study the effects of disease-associated PTPN11 alleles, we generated transgenic fruitflies with GAL4-inducible expression of wild-type or mutant csw, the Drosophila orthologue of PTPN11. All three transgenic mutant CSWs rescued a hypomorphic csw allele's eye phenotype, documenting activity. Ubiquitous expression of two strong csw mutant alleles were lethal, but did not perturb development from some CSW-dependent receptor tyrosine kinase pathways. Ubiquitous expression of the weaker N308D allele caused ectopic wing veins, identical to the EGFR GOF phenotype. Epistatic analyses established that csw(N308D)'s ectopic wing vein phenotype required intact EGF ligand and receptor, and that this transgene interacted genetically with Notch, DPP and JAK/STAT signaling. Expression of the mutant csw transgenes increased RAS-MAP kinase activation, which was necessary but not sufficient for transducing their phenotypes. The findings from these fly models provided hypotheses testable in mammalian models, in which these signaling cassettes are largely conserved. In addition, these fly models can be used for sensitized screens to identify novel interacting genes as well as for high-throughput screening of therapeutic compounds for NS and PTPN11-related cancers.
Hum Mol Genet 2006 Feb 15
PMID:Transgenic Drosophila models of Noonan syndrome causing PTPN11 gain-of-function mutations. 1639 95

Vascular endothelial growth factor (VEGF) is a main factor promoting neovascularization (angiogenesis) of solid tumours as prostate carcinoma. Hypoxia stimulates VEGF gene expression by activating the hypoxia-inducible factor-1 (HIF-1alpha). In the present study, the hypoxia-mimicking agent Ni(2+) induced vasoactive intestinal peptide (VIP) expression at both mRNA and peptide levels but it did not modify the expression of VIP receptors (VPAC(1), VPAC(2) and PAC(1) receptors) in androgen-dependent human LNCaP prostate cancer cells. VIP increased the mRNA levels of VPAC(1) and PAC(1) receptors whereas it decreased VPAC(2) receptor mRNA level. These features support that hypoxia up-regulation of VIP gene expression in prostatic carcinoma may lead to VIP regulation of the expression of its receptors by means of autocrine/paracrine mechanisms. Either VIP or hypoxia mimetics with Ni(2+) increased VEGF expression whereas both conditions together resulted in an additive response. It suggests two independent mechanisms for the observed pro-angiogenic activities of VIP and hypoxia. VIP did not stimulate HIF-1alpha mRNA expression but increased the translocation of HIF-1alpha from the cytosolic compartment to the cell nucleus. Moreover, VIP was unable to modify the expression of the HIF-1alpha inhibitor FIH-1 discarding the possibility of an indirect effect of VIP on HIF-1 transactivation.
Mol Cell Endocrinol 2006 Apr 25
PMID:Hypoxia regulation of expression and angiogenic effects of vasoactive intestinal peptide (VIP) and VIP receptors in LNCaP prostate cancer cells. 1656 10


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