Medicines and promoting

The transcription factor serum response factor (SRF) regulates expression of growth factor-dependent genes and muscle-specific genes in vertebrates. Homologous factors regulate differentiation of some ectodermic tissues in invertebrates. To explore the molecular basis of these different physiological functions, the functionality of human, Drosophila melanogaster and Artemia franciscana SRFs in mammalian cells has been compared in this article. D. melanogaster and, to a lesser extend, A.

9p system191 01-06-2013 32 5   Download

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

The insect ecdysteroid receptor consists of a heterodimer between EcR and the RXR-orthologue, USP. We addressed the question of whether this heterodimer, like all other RXR heterodimers, may be formed in the absence of ligand and whether ligand promotes dimerization. We found that C-terminal protein fragments that comprised the ligand binding, but not the DNA binding domain of EcR and USP and which were equipped with the activation or DNA binding region of GAL4, respectively, exhibit a weak ability to interact spontaneously with each other.

9p system191 01-06-2013 29 3   Download

An immuno-homologue of maize Ca2+/calmodulin (CaM)dependent protein kinase with a molecular mass of 72 kDa was identified in pea. The pea kinase (PsCCaMK) was upregulated in roots in response to low temperature and increased salinity. Exogenous Ca2+ application increased the kinase level and the response was faster than that obtained following stress application. Low temperaturemediated, but not salinity-mediated stress kinase increase was inhibited by the application of EGTA and W7, a CaM inhibitor....

12p system191 01-06-2013 39 5   Download

SHP-1, a protein-tyrosine phosphatase with two srchomology 2 domains, is expressed predominantly in hematopoietic and epithelial cells and has been implicated in numerous signaling pathways as a negative regulator. Two promoters direct the expression of human and murine SHP-1, and two types of transcripts (I) and (II) SHP-1, are initiated from each of these promoters. The cDNA sequences of (I)SHP-1 and (II)SHP-1 are identical except in the 5¢ untranslated region and in the first few coding nucleotides.

8p system191 01-06-2013 36 3   Download

The Sp family is a family of transcription factors that bind to cis-elements in the promoter regions of various genes. Regulation of transcription by Sp proteins is based on interactions between a GC-rich binding site (GGGCGG) in DNA and C-terminal zinc finger motifs in the proteins. In this study, we characterized the GC-rich promoter of the gene for the DNA methyltransferase (Dnmt1) that is responsible for methylation of cytosine residues in mammals and plays a role in gene silencing.

10p system191 01-06-2013 38 4   Download

Mitochondrial functional and structural impairment and generation of oxidative stress have been implicated in aging, various diseases and chemotherapies. This study analyzed azidothymidine (AZT)-caused failures in mitochondrial functions, in redox regulation and activation of the HIV-1 gene expression. We monitored intracellular concentrations of ATP and glutathione (GSH) as the indicators of energy production and redox conditions, respectively, during the time-course experiments with U937 and MOLT4 human lymphoid cells in the presence of AZT (0.05 mgÆmL)1) or H2O2 (0.01 mM) for 15–25 days.

7p system191 01-06-2013 42 3   Download

Selenoprotein P (SeP) is a plasma protein that contains up to 10 selenocysteine residues and accounts for about 50% of total selenium in human plasma. We have previously shown that SeP expression in the human liver cell line HepG2 is inhibited by transforming growth factor (TGF)-b1 on a transcriptional level. Smad proteins are the transcriptional mediators of TGF-b signalling and putative Smad-binding elements (SBE) comprising the core sequence CAGACA are present at two positions in the SeP promoter....

6p system191 01-06-2013 35 4   Download

Connective tissue growth factor/hypertrophic chondrocyte specific gene product 24 (CTGF/Hcs24) promotes proliferation and differentiation of chondrocytes in culture. We investigated the roles of two major types of mitogen activated protein kinase (MAPK) in the promotion of proliferation and differentiation by CTGF/Hcs24. Here we report the effects of the MAPKK/MEK 1/2 inhibitor, PD098059, and p38 MAPK inhibitor, SB203580, in a human chondrosarcoma-derived chondrocytic cell line (HCS-2/8) and rabbit growth cartilage (RGC) cells treated with CTGF/ Hcs24....

8p system191 01-06-2013 40 3   Download

The 5¢ flanking region of the bile salt export pump (Bsep) gene was systematically analysed to provide the basis for understanding the mechanisms which regulate Bsep transcription. In addition substrates and drugs were investigated for their ability to alter Bsep promoter activity. Bsep promoter function was restricted to hepatocyte derived HepG2 cells. The 5¢ deletional analysis revealed a biphasic shape of reporter gene activities, indicating a suppressive element between nucleotides )800 and )512. ...

9p research12 01-06-2013 38 4   Download

Wilson disease (WD), an inherited disorder affecting copper metabolism, is characterized by hepatic cirrhosis and neuronal degeneration, which result from toxic levels of copper that accumulate in the liver and brain, respectively. We reported previously that the  1.3-kb promoter of the WD gene contains four metal response elements (MREs). Among the four MREs, MREa plays the most important role in the transcriptional activation of the WD promoter.

11p research12 01-06-2013 53 3   Download

To search for novel regulatory regions, we examined the features of chromatin structure in the rat B29/Ig-b gene and its flanking regions by determining DNase I hypersensitive sites (DHS) in plasmacytoma-derived Y3 cells. Six Y3 cellspecific DHS were detected at )8.6, promoter, +0.7, +4.4, +6.0, and +8.7 kb. The DHS at +4.4, +6.0, and +8.7 kb were present in the intergenic region between B29/Ig-b and growth hormone (GH) genes and were mapped inside conserved sequences in rat and humans.

10p research12 01-06-2013 29 4   Download

Retinoids are potent immune modulators that inhibit Fas ligand (FasL) expression and thereby repress the activationinduced apoptosis of immature thymocytes and T-cell hybridomas. In this study, we demonstrate that all-transretinoic acid (all-trans-RA) directly represses the transcriptional activity of the nuclear factors of activated T-cells (NFAT), which is an important transactivator of the FasL promoter.

9p research12 01-06-2013 42 5   Download

Insulin-like growth factor (IGF) binding to the type 1 IGF receptor (IGF1R) elicits mitogenic e€ects, promotion of di€erentiation and protection from apoptosis. This study has systematically measured IGF1R binding anities of IGF-I, IGF-II and 14 IGF analogues to a recombinant high-anity form of the IGF1R using BIAcore technology. The analogues assessed could be divided into two groups: (a) those designed to investigate binding of IGF-binding protein, which exhibited IGF1R-binding anities similar to those of IGF-I or IGF-II;...

8p research12 01-06-2013 40 4   Download

Matrilysin (matrix metalloproteinase-7) plays important roles in tumor progression. It was previously found that matrilysin binds to the surface of colon cancer cells to promote their metastatic potential. In this study, we identified annexin II as a novel membrane-bound substrate of matrilysin. Treatment of human colon cancer cell lines with active matrilysin released a 35 kDa annexin II form, which lacked its N-terminal region, into the culture supernatant. The release of the 35 kDa annexin II by matrilysin was significantly enhanced in the presence of serotonin or heparin....

14p research12 29-04-2013 41 2   Download

Obesity is a central feature of the metabolic syndrome and is associated with increased risk for insulin resistance and type II diabetes. Here, we investigated the contribution of human apoliprotein E3 and mouse apoli-protein E to the development of diet-induced obesity in response to western-type diet. Our data show that apolipoprotein E contributes to the development of obesity and other related metabolic disorders, and that human apolipoprotein E3 is more potent than mouse apolipoprotein E in promoting obesity in response to western-type diet. ...

14p research12 29-04-2013 46 3   Download

Heat shock transcription factors (HSFs) are characterized by their ability, upon activation, to bind to heat shock response elements (HSE) present in the promoter of their target genes. HSE are composed of inverted repeats of the pentamer nGAAm. In this study, we compare the embryonic HSF2 protein, purified from F9 embryonal carcinoma cells tumor, and thein vitro synthesized HSF2. We show that the context of HSF2 synthesis influences its thermosensitivity and DNA-binding properties.

11p research12 29-04-2013 47 2   Download

Mitochondrial uncoupling protein 1 (UCP1) is a speci®c marker of multilocular brown adipocytes. Ectopic UCP1 in white fat of aP2-Ucp1micemitigates development of obesity byboth, increasing energy expenditure anddecreasingin situ lipogenesis. In order to further analyse consequences of respiratory uncoupling inwhite fat, the e€ects of the ectopic UCP1 on the morphology of adipocytes and biogenesis of mitochondria in these cells were studied.

10p research12 29-04-2013 40 4   Download

The promoter of the early growth response gene (Egr-1) has been described to be activated by ionizing radiation, and it seems to be clear that this process involves di€erent mitogen activated protein (MAP) kinases, dependent on the speci®c cell type examined. However, early steps leading to activation of the corresponding pathways and thus to overexpression of Egr-1 are not well understood.

10p research12 29-04-2013 45 2   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