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)

In angiosperms, lignin is built from two main monomers, coniferyl and sinapyl alcohol, which are incorporated respectively as G and S units in the polymer. The last step of their synthesis has so far been considered to be performed by a family of dimeric cinnamyl alcohol dehydrogenases (CAD2). However, previous studies on Eucalyptus gunnii xylem showed the presence of an additional, structurally unrelated, monomeric CAD form named CAD1. This form reduces coniferaldehyde to coniferyl alcohol, but is inactive on sinapaldehyde. In this paper, we report the functional characterization of CAD1 in tobacco (Nicotiana tabacum L.). Transgenic tobacco plants with reduced CAD1 expression were obtained through an RNAi strategy. These plants displayed normal growth and development, and detailed biochemical studies were needed to reveal a role for CAD1. Lignin analyses showed that CAD1 down-regulation does not affect Klason lignin content, and has a moderate impact on G unit content of the non-condensed lignin fraction. However, comparative metabolic profiling of the methanol-soluble phenolic fraction from basal xylem revealed significant differences between CAD1 down-regulated and wild-type plants. Eight compounds were less abundant in CAD1 down-regulated lines, five of which were identified as dimers or trimers of monolignols, each containing at least one moiety derived from coniferyl alcohol. In addition, 3-trans-caffeoyl quinic acid accumulated in the transgenic plants. Together, our results support a significant contribution of CAD1 to the synthesis of coniferyl alcohol in planta, along with the previously characterized CAD2 enzymes.
Plant Mol Biol 2005 Nov
PMID:Metabolite profiling reveals a role for atypical cinnamyl alcohol dehydrogenase CAD1 in the synthesis of coniferyl alcohol in tobacco xylem. 1627 Feb 28

We analyzed a combined data set of two protein-coding nuclear genes (CAD and RNA polymerase II) and a nuclear ribosomal gene (28S D2-D4 region) for 68 bee species and 11 wasp outgroups. Our taxon sampling included all seven extant bee families, 17 of 20 subfamilies, and diverse tribes. Wasp outgroups included the two families most closely related to bees: Crabronidae and Sphecidae. We analyzed the combined and single gene data sets using parsimony and Bayesian methods, which yielded largely congruent results. Our results provide reasonably strong support for family and subfamily-level relationships among bees. Our data set strongly supports the sister-group relationship of the Colletidae and Stenotritidae, and places Halictidae as sister to this clade combined. Our analyses place the Melittidae and the long-tongued (LT) bee clade (Apidae+Megachilidae) near the base of the tree with Colletidae (and Stenotritidae) in a fairly highly derived position. This topology ("Melittidae-LT basal") was obtained in previous morphological studies under certain methods of character coding. A more widely accepted tree topology that places Colletidae (and/or Stenotritidae) as sister to all other bees ("Colletidae basal") is not supported by our data. The "Melittidae-LT basal" hypothesis may better explain patterns in the bee fossil record as well as historical biogeography of certain bee groups. Our results provide new insights into higher-level bee phylogeny and indicate that CAD, RNA polymerase II, and 28S are useful data sets for resolving Cretaceous-age divergences in bees and other Hymenoptera.
Mol Phylogenet Evol 2006 May
PMID:Analysis of family-level relationships in bees (Hymenoptera: Apiformes) using 28S and two previously unexplored nuclear genes: CAD and RNA polymerase II. 1641 68

Positron emission tomography (PET) is an investigative tool that has allowed unprecedented in vivo quantification of physiologic processes including myocardial perfusion and metabolism. Several technical features make PET an ideal technology for the noninvasive evaluation of cardiac physiology. The exponential growth in the number of PET cameras worldwide, offers new opportunities for cardiac applications of PET. Moreover, the integration of PET and multidetector CT (PET/CT) technology will likely accelerate the clinical use of this modality in cardiology for revealing the degree and location of anatomic stenoses and their physiologic significance, the atherosclerotic plaque burden and its composition. Integrated PET/CT is a powerful noninvasive modality to establish the diagnosis, define risk, and guide management with a single study of CAD patients.
Q J Nucl Med Mol Imaging 2006 Mar
PMID:Integrated PET/CT for cardiac imaging. 1655 3

Curcumin is a natural pigment that has been shown to induce cell death in many cancer cells; however, the death mode depends on the cell type and curcumin concentration. Here we show that, in Jurkat cells, 50 micromol/L curcumin severely lowers cell survival and induces initial stage of chromatin condensation. It also induces caspase-3, which is sufficient to cleave DNA fragmentation factor 45 [DFF45/inhibitor of caspase-activated DNase (ICAD)], the inhibitor of DFF40/CAD endonuclease. However, the release of DFF40/CAD from its inhibitor does not lead to oligonucleosomal DNA degradation in curcumin-treated cells. Moreover, curcumin treatment protects cells from UVC-induced oligonucleosomal DNA degradation. In biochemical experiments using recombinant DFF activated with caspase-3, we show that curcumin inhibits plasmid DNA and chromatin degradation although it does not prevent activation of DFF40/CAD endonuclease after its release from the inhibitor. Using DNA-binding assay, we show that curcumin does not disrupt the DNA-DFF40/CAD interaction. Instead, molecular modeling indicates that the inhibitory effect of curcumin on DFF40/CAD activity results from curcumin binding to the active center of DFF40/CAD endonuclease.
Mol Cancer Ther 2006 Apr
PMID:Curcumin induces caspase-3-dependent apoptotic pathway but inhibits DNA fragmentation factor 40/caspase-activated DNase endonuclease in human Jurkat cells. 1664 63

In cells of neural and non-neural origin, tubulin forms a complex with plasma membrane Na(+),K(+)-ATPase, resulting in inhibition of the enzyme activity. When cells are treated with 1 mM L-glutamate, the complex is dissociated and enzyme activity is restored. Now, we found that in CAD cells, ATPase is not activated by L-glutamate and tubulin/ATPase complex is not present in membranes. By investigating the causes for this characteristic, we found that tubulin must be acetylated in order to associate with ATPase and to inhibit its catalytic activity. In CAD cells, the acetylated tubulin isotype is absent. Treatment of CAD cells with deacetylase inhibitors (trichostatin A or tubacin) caused appearance of acetylated tubulin, formation of tubulin/ATPase complex, and reduction of membrane ATPase activity. In these treated cells, addition of 1 mM L-glutamate dissociated the complex and restored the enzyme activity. Cytosolic tubulin from trichostatin A-treated but not from non-treated cells inhibited ATPase activity. These findings indicate that the acetylated isotype of tubulin is required for interaction with membrane Na(+),K(+)-ATPase and consequent inhibition of enzyme activity.
Mol Cell Biochem 2006 Oct
PMID:Tubulin must be acetylated in order to form a complex with membrane Na(+),K (+)-ATPase and to inhibit its enzyme activity. 1673 2

Leptin plays an important role in satiety signaling and is related to obesity. Variants of leptin gene (LEP) have been associated to differences in plasma leptin levels and obesity-related phenotypes. The purpose of this study was to evaluate the association of LEP 3'HVR and leptin concentrations and obesity-related traits in our population. Anthropometrics and systolic/diastolic pressure were measured in 210 unrelated Brazilian individuals. Blood samples were collected for quantification of leptin, glucose and lipids and DNA extraction. LEP 3'HVR polymorphic region was amplified by PCR and fragments were analyzed by polyacrylamide gel electrophoresis. Obesity was associated with hypertension, hyperglycemia, obesity-related traits, plasma leptin and serum lipids (p < 0.05). The frequency of LEP 3'HVR class I alleles (I/I + I/II genotypes) was higher in obese (p = 0.043) than in non-obese individuals. Multivariate logistic regression showed that the risk for obesity is nine times higher in hypertensive individuals and two times higher in class I alleles carriers. The presence of class I alleles was associated with increased BMI and WC. Plasma leptin was related to class I alleles in women (p < 0.05). No association was found between LEP 3'HVR and hypertension or risk factors for CAD in our sample. Our results suggest that LEP 3'HVR is an important predictor for obesity-related traits and leptin plasma levels.
Mol Genet Metab 2006 Dec
PMID:LEP 3'HVR is associated with obesity and leptin levels in Brazilian individuals. 1676 76

Our goal is to understand the pathogenesis of amyloid-beta (Abeta) deposition in the Alzheimer's disease (AD) brain. We established a cell culture system where central nervous system-derived neuronal cells (CAD cells) produce and accumulate within their processes large amounts of Abeta peptide, similar to what is believed to occur in brain neurons, in the initial phases of AD. Using this system, we show that accumulation of Abeta begins within neurites, prior to any detectable signs of neurodegeneration or abnormal vesicular transport. Neuritic accumulation of Abeta is restricted to a small population of neighboring cells that express normal levels of amyloid-beta precursor protein (APP) but show redistribution of BACE1 to the processes, where it colocalizes with Abeta and markers of late endosomes. Consistently, cells that accumulate Abeta appear in isolated islets, suggesting their clonal origin from a few cells that show a propensity to accumulate Abeta. These results suggest that Abeta accumulation is initiated in a small number of neurons by intracellular determinants that alter APP metabolism and lead to Abeta deposition and neurodegeneration. CAD cells appear to recapitulate the biochemical processes leading to Abeta deposition, thus providing an experimental in vitro system for studying the molecular pathobiology of AD.
Mol Cell Biol 2006 Jul
PMID:Neuritic deposits of amyloid-beta peptide in a subpopulation of central nervous system-derived neuronal cells. 1678 85

Mechanisms coordinating neural progenitor cell cycle exit and differentiation are incompletely understood. The cyclin-dependent kinase inhibitor p27(Kip1) is transcriptionally induced, switching specific neural progenitors from proliferation to differentiation. However, neuronal differentiation-specific transcription factors mediating p27(Kip1) transcription have not been identified. We demonstrate the homeodomain transcription factor Phox2a, required for central nervous system (CNS)- and neural crest (NC)-derived noradrenergic neuron differentiation, coordinates cell cycle exit and differentiation by inducing p27(Kip1) transcription. Phox2a transcription and activation in the CNS-derived CAD cell line and primary NC cells is mediated by combined cyclic AMP (cAMP) and bone morphogenetic protein 2 (BMP2) signaling. In the CAD cellular model, cAMP and BMP2 signaling initially induces proliferation of the undifferentiated precursors, followed by p27(Kip1) transcription, G(1) arrest, and neuronal differentiation. Small interfering RNA silencing of either Phox2a or p27(Kip1) suppresses p27(Kip1) transcription and neuronal differentiation, suggesting a causal link between p27(Kip1) expression and differentiation. Conversely, ectopic Phox2a expression via the Tet-off expression system promotes accelerated CAD cell neuronal differentiation and p27(Kip1) transcription only in the presence of cAMP signaling. Importantly, endogenous or ectopically expressed Phox2a activated by cAMP signaling binds homeodomain cis-acting elements of the p27(Kip1) promoter in vivo and mediates p27(Kip1)-luciferase expression in CAD and NC cells. We conclude that developmental cues of cAMP signaling causally link Phox2a activation with p27(Kip1) transcription, thereby coordinating neural progenitor cell cycle exit and differentiation.
Mol Cell Biol 2006 Dec
PMID:Homeodomain transcription factor Phox2a, via cyclic AMP-mediated activation, induces p27Kip1 transcription, coordinating neural progenitor cell cycle exit and differentiation. 1698 76

Norepinephrine (NE) transporters (NETs) are high-affinity transport proteins that mediate the synaptic clearance of NE after vesicular release. NETs represent a major therapeutic target for antidepressants and are targets of multiple psychostimulants including amphetamine (AMPH) and cocaine. Recently, we demonstrated that syntaxin 1A (SYN1A) regulates NET surface expression and, through binding to the transporter's NH(2) terminus, regulates transporter catalytic function. AMPH induces NE efflux and may also regulate transporter trafficking. We monitored NET distribution and function in catecholaminergic cell lines (CAD) stably transfected with either full-length human NET (CAD-hNET) or with an hNET N-terminal deletion (CAD-hNETDelta(28-47) cells). In hNET-CAD cells, AMPH causes a slow and small reduction of surface hNET with a modest increase in hNET/SYN1A associations at the plasma membrane. In contrast, in CAD-hNETDelta(28-47) cells, AMPH induces a rapid and substantial reduction in surface hNETDelta(28-47) accompanied by a large increase in plasma membrane hNETDelta(28-47)/SYN1A complexes. We also found that AMPH in CAD-hNETDelta(28-47) cells induces a robust increase in cytosolic Ca2+ and concomitant activation of calcium/calmodulin-dependent protein kinase II (CaMKII). Inhibition of either the increase in intracellular Ca2+ or CaMKII activity blocks AMPH-stimulated hNETDelta(28-47) trafficking and the formation of hNETDelta(28-47)/SYN1A complexes. Here, we demonstrate that AMPH stimulation of CAMKII stabilizes an hNET/SYN1A complex. This hNET/SYN1A complex rapidly redistributes, upon AMPH treatment, when mechanisms supported by the transporter's NH2 terminus are eliminated.
Mol Pharmacol 2007 Jan
PMID:Amphetamine induces a calcium/calmodulin-dependent protein kinase II-dependent reduction in norepinephrine transporter surface expression linked to changes in syntaxin 1A/transporter complexes. 1703 5

The first formal analysis of phylogenetic relationships among small-headed flies (Acroceridae) is presented based on DNA sequence data from two ribosomal (16S and 28S) and two protein-encoding genes: carbomoylphosphate synthase (CPS) domain of CAD (i.e., rudimentary locus) and cytochrome oxidase I (COI). DNA sequences from 40 species in 22 genera of Acroceridae (representing all three subfamilies) were compared with outgroup exemplars from Nemestrinidae, Stratiomyidae, Tabanidae, and Xylophagidae. Parsimony and Bayesian simultaneous analyses of the full data set recover a well-resolved and strongly supported hypothesis of phylogenetic relationships for major lineages within the family. Molecular evidence supports the monophyly of traditionally recognised subfamilies Philopotinae and Panopinae, but Acrocerinae are polyphyletic. Panopinae, sometimes considered "primitive" based on morphology and host-use, are always placed in a more derived position in the current study. Furthermore, these data support emerging morphological evidence that the type genus Acrocera Meigen, and its sister genus Sphaerops, are atypical acrocerids, comprising a sister lineage to all other Acroceridae. Based on the phylogeny generated in the simultaneous analysis, historical divergence times were estimated using Bayesian methodology constrained with fossil data. These estimates indicate Acroceridae likely evolved during the late Triassic but did not diversify greatly until the Cretaceous.
Mol Phylogenet Evol 2007 Jun
PMID:Phylogeny and Bayesian divergence time estimations of small-headed flies (Diptera: Acroceridae) using multiple molecular markers. 1719 37


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