Causes of cancer

Human immunodeficiency virus type 1 protein R (HIV-1 Vpr) promotes nuclear entry of viral nucleic acids in nondividing cells, causes G2 cell cycle arrest and is involved in cellular differentiation and cell death. Vpr subcellular localization is as variable as its functions. It is known, that consistent with its role in nuclear transport, Vpr localizes to the nuclear envelope of human cells. Further, a reported ion channel activity of Vpr is clearly dependent on its localization in or at membranes.

6p system191 01-06-2013 33 4   Download

We have examined the effects of widely used stress-inducing agents on protein synthesis and on regulatory components of the translational machinery. The three stresses chosen, arsenite, hydrogen peroxide and sorbitol, exert their effects in quite different ways. Nonetheless, all three rapidly ( 30 min) caused a profound inhibition of protein synthesis. In each case this was accompanied by dephosphorylation of the eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and increased binding of this repressor protein to eIF4E. ...

10p system191 01-06-2013 44 4   Download

Thea3b1 integrin is an adhesion receptor for extracellular matrix proteins including isoforms of laminin, and the changes of its expression level in various cancer cells are thought to cause their malignant phenotypes. We have cloned an approximately 4 kb DNA fragment of the 5¢-flanking region of the murinea3 integrin gene and analyzed its promoter activity.

9p research12 23-04-2013 36 3   Download

The calcium-sensing receptor (CaR) belongs to family C of the G-protein coupled receptor superfamily. The receptor is believed to exist as a homodimer due to covalent and non-covalent interactions between the two amino terminal domains (ATDs). It is well established that agonist binding to family C receptors takes place at the ATD and that this causes theATDdimer to twist.However, very little isknown about the translationof theATDdimer twist intoG-protein coupling to the 7 transmembrane moieties (7TMs) of these receptor dimers....

12p tumor12 22-04-2013 40 2   Download

The different roles of ubiquinone-10 (UQ10) at the primary and secondary quinone (QAand QB) binding sites ofRho-dobacter sphaeroidesR26 reaction centres are governed by the protein microenvironment. The 4C¼O carbonyl group of QAis unusually strongly hydrogen-bonded, in contrast to QB. This asymmetric binding seems to determine their dif-ferent functions. The asymmetric hydrogen-bonding at QA can be caused intrinsically by distortion of the methoxy groups or extrinsically by binding to specific amino-acid side groups. ...

7p tumor12 20-04-2013 32 2   Download

Several clinical trialshave revealed that individualswhowere givenb)carotene and vitamin Adid not have a reduced risk of cancer compared to those given placebo 2,3 ; 2,3 rather, vita-min A could actually have caused an adverse effect in the lungs of smokers [Omenn, G.S., Goodman, G.E., Thorn-quist, M.D., Balmes, J., Cullen, M.R., Glass, A., Keogh, J.P., Meyskens, F.L., Valanis, B., Williams, J.H., Barnhart, S. & Hammar, S.N. Engl. J. Med(1996) 334, 1150–1155; Hennekens, C.H., Buring, J.E.,Manson, J.E., Stampfer,M., Rosner,B.,Cook,N.R.,Belanger,C.,LaMotte,F.,Gazi-ano, J.M., Ridker, P.M.

9p tumor12 20-04-2013 37 2   Download

A large number of bioactive peptides have been isolated from amphibian skin secretions. These peptides have a variety of actions including antibiotic and anticancer acti-vities and the inhibition of neuronal nitric oxide synthase. We have investigated the structure–activity relationship of citropin 1.1, a broad-spectrum antibiotic and anticancer agent that also causes inhibition of neuronal nitric oxide synthase, by making a number of synthetically modified analogues.

13p tumor12 20-04-2013 37 3   Download

We have studied the reaction native«denatured for the 33-kDa protein isolated from photosystem II. Sucrose and glycerol have profound effects on pressure-induced unfolding. The additives shift the equilibrium to the left; they also cause a significant decrease in the standard volume change (DV). The change in DVwas related to the sucrose and glycerol concentrations.

8p fptmusic 16-04-2013 59 5   Download

InEscherichia colithe codons CGG, AGG, UGG or GGG (NGG codons) but not GGN or GNG (where N is non-G) are associated with low expres-sion of a reporter gene, if located at positions +2 to +5. Induction of a lacZ reporter gene with any one of the NGG codons at position +2 to +5 does not influence growth of a normal strain, but growth of a strain with a defective peptidyl-tRNA hydrolase (Pth) enzyme is inhibited.

11p fptmusic 12-04-2013 43 2   Download

Whereas the majority of disease-related mitochondrial DNA mutations exhibit significant biochemical and clinical heterogeneity, mutations within the mitochondrially encoded human cytochrome b gene (MTCYB) are almost exclusively associated with isolated complex III deficiency in muscle and a clinical presentation involving exercise intolerance.

10p fptmusic 11-04-2013 35 3   Download

In recent studies on heme-copper oxidases a particular glutamate residue in subunit II has been suggested to constitute the entry point of the so-called K pathway. In contrast, mutations of this residue (E78 II ) in the Paracoccus denitrificanscytochromecoxidase do not affect its catalytic activity at all (E78 II Q) or reduce it to about 50% (E78 II A); in the latter case, the mutation causes no drastic decrease in hemea3 reduction kinetics under anaerobic con-ditions, when compared to typical K pathway mutants....

9p awards 05-04-2013 29 4   Download

Spinocerebellar ataxia types 2 (SCA2) and 3 (SCA3) are autosomal-dominantly inherited, neurodegenerative dis-eases caused by CAG repeat expansions in the coding regions of the genes encoding ataxin-2 and ataxin-3, respectively. To provide a rationale for further functional experiments, we explored the proteinarchitectures of ataxin-2 and ataxin-3. Using structure-based multiple sequence alignments of homologous proteins, we investigated domains, sequence motifs, and interaction partners.

16p awards 05-04-2013 49 5   Download

Information on the regulation and structure–function rela-tion of enzymes involved in DNA precursor synthesis is pivotal, as defects in several of these enzymes have been found to cause depletion or deletion of mitochondrial DNA resulting in severediseases.Here, the effect of aminoacid106 on the enzymatic properties of the cell-cycle-regulated human cytosolic thymidine kinase 1(TK1) is investigated.

9p dell39 03-04-2013 51 4   Download

Loss of functional emerin, a nuclear membrane protein, causes X-linked recessive Emery–Dreifuss muscular dystro-phy. In a yeast two-hybrid screen, we found that emerin interacts with Btf, a death-promoting transcriptional repressor, which is expressedat high levels in skeletalmuscle. Biochemical analysis showed that emerin binds Btf with an equilibriumaffinity (KD)of100 nM. Using a collection of 21 clustered alanine-substitution mutations in emerin, the resi-dues required for binding to Btf mapped to two regions of emerin that flank its lamin-binding domain. ...

11p dell39 03-04-2013 28 4   Download

A small deletion in the second intron of humanNDUFV2 (IVS2+5_+8delGTAA) has been shown to cause hyper-trophic cardiomyopathy and encephalomyopathy [Be´nit, P., Beugnot, R., Chretien, D., Giurgea, I., de Lonlay-Debeney, P., Issartel, J.P., Kerscher, S., Rustin, P., Ro¨tig, A. & Munnich, A. (2003)Human Mutat.21, 582–586]. Skipping of exon 2 results in a partial deletion of the mitochondrial targeting sequence of the precursor for the 24 kDa subunit of respiratory chain complex I.

8p dell39 03-04-2013 45 4   Download

Human airway trypsin-like protease (HAT), a serine protease found in the sputum of patients with chronic airway diseases, is an agonist of protease-activated receptor-2 (PAR-2). Previous results have shown that HAT enhances the release of amphiregulin (AR); further, it causes MUC5AC gene expression through the AR-epidermal growth factor receptor pathway in the airway epithelial cell line NCI-H292.

13p dell39 27-03-2013 34 1   Download

We found that benomyl, a benzimidazole fungicide, strongly suppressed the reassembly of cold-depolymerized spindle microtubules in HeLa cells. Benomyl perturbed microtubule-kinetochore attachment and chromosome alignment at the metaphase plate. Benomyl also significantly decreased the distance between the sister kinetochore pairs in metaphase cells and increased the level of the checkpoint protein BubR1 at the kinetochore region, indicating that benomyl caused loss of tension across the kineto-chores....

15p inspiron33 25-03-2013 37 3   Download

We investigated the survival signals of epidermal growth factor (EGF) in human gastric adenocarcinoma cell line TMK-1. Treatment of TMK-1 cells with adriamycin (ADR) caused apoptosis and apoptosis-related reactions such as the release of cytochromecfrom mitochondria and the activation of caspase 9.

13p inspiron33 25-03-2013 42 2   Download

Primary cultured fibroblasts of four patients with idiopathic short stature and severe growth delay, which displayed normal growth hormone receptor expression presented a reduced ability for activation of signal transducer and activator of transcription-3 (STAT3). Impaired STAT3 activation was accompanied by cell-cycle arrest at the Go⁄G1 phase.

13p inspiron33 25-03-2013 44 2   Download

Recurrent missense fibroblast growth factor receptor 3 (FGFR3) mutations have been ascribed to skeletal dysplasias of variable severity including the lethal neonatal thanatophoric dysplasia types I (TDI) and II (TDII). To elucidate the role of activating mutations causing TDI on receptor traffick-ing and endocytosis, a series of four mutants located in different domains of the receptor were generated and transiently expressed.

11p galaxyss3 19-03-2013 36 4   Download