Effects of mutant p53 expression on human 15-lipoxygenase-promoter activity and murine 12/15-lipoxygenase gene expression: evidence that 15-lipoxygenase is a mutator gene.

Abstract:

:Human 15-lipoxygenase (h15-LO) is present on chromosome 17p13.3 in close proximity to the tumor-suppressor gene, p53. 15-LO is implicated in antiinflammation, membrane remodeling, and cancer development/metastasis. The murine BALB/c embryo fibroblast cell line, (10)1val, expresses p53 in mutant (mt) conformation when grown at 39 degrees C and in wild-type conformation when grown at 32 degrees C. Transfection of h15-LO promoter constructs (driving luciferase reporter) into (10)1val cells and into p53-deficient (10)1 cells resulted in a marked increase in h15-LO promoter activity in (10)1val cells at 39 degrees C, but not at 32 degrees C, or as compared with (10)1 cells. Transfection of h15-LO promoter deletion constructs, however, resulted in total loss of activity in both cell types at 32 degrees C and 39 degrees C. Cotransfection of (10)1 cells with h15-LO promoter (driving luciferase reporter) along with increasing levels of a mt p53 expression vector demonstrated dose-dependent capacity of mt p53 to induce 15-LO promoter activity. No effect was observed with wild-type p53. In contrast to h15-LO promoter activity, (10)1val cells had significantly lower levels of endogenous (murine) 12/15-LO (mouse analog of h15-LO) mRNA and protein when grown at 39 degrees C compared with cells grown at 32 degrees C. Our data support the hypothesis that loss of a tumor-suppressor gene (p53), or "gain-of-function activities" resulting from the expression of its mutant forms, regulates 15-LO promoter activity in man and in mouse, albeit in directionally opposite manners. The studies define a direct link between 15-LO activity and an established tumor-suppressor gene located in close chromosomal proximity.

authors

Kelavkar UP,Badr KF

doi

10.1073/pnas.96.8.4378

keywords:

subject

Has Abstract

pub_date

1999-04-13 00:00:00

pages

4378-83

issue

8

eissn

0027-8424

issn

1091-6490

journal_volume

96

pub_type

杂志文章
  • Mutagenesis by the autoxidation of iron with isolated DNA.

    abstract::Oxygen free radicals are highly reactive species generated by many cellular oxidation-reduction processes. These radicals damage cellular constituents and have been causally implicated in the pathogenesis of many human diseases. We report here that oxygen free radicals generated by Fe2+ in aqueous solution are mutagen...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.11.3918

    authors: Loeb LA,James EA,Waltersdorph AM,Klebanoff SJ

    更新日期:1988-06-01 00:00:00

  • Functional heterogeneity of the four voltage sensors of a human L-type calcium channel.

    abstract::Excitation-evoked Ca(2+) influx is the fastest and most ubiquitous chemical trigger for cellular processes, including neurotransmitter release, muscle contraction, and gene expression. The voltage dependence and timing of Ca(2+) entry are thought to be functions of voltage-gated calcium (CaV) channels composed of a ce...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1411127112

    authors: Pantazis A,Savalli N,Sigg D,Neely A,Olcese R

    更新日期:2014-12-23 00:00:00

  • RNA polymerase idling and clearance in gal promoters: use of supercoiled minicircle DNA template made in vivo.

    abstract::We have developed an in vivo system to engender supercoiled "minicircle" DNA containing a single promoter by using the integrative recombination system of bacteriophage lambda. The resulting minicircle templates allow quantitative analysis of the stages of transcription initiation from a promoter, including synthesis ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.2.472

    authors: Choy HE,Adhya S

    更新日期:1993-01-15 00:00:00

  • A viral regulator of glycoprotein complexes contributes to human cytomegalovirus cell tropism.

    abstract::Viral glycoproteins mediate entry of enveloped viruses into cells and thus play crucial roles in infection. In herpesviruses, a complex of two viral glycoproteins, gH and gL (gH/gL), regulates membrane fusion events and influences virion cell tropism. Human cytomegalovirus (HCMV) gH/gL can be incorporated into two dif...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1419875112

    authors: Li G,Nguyen CC,Ryckman BJ,Britt WJ,Kamil JP

    更新日期:2015-04-07 00:00:00

  • Structural changes and metal binding by proalbumins and other amino-terminal genetic variants of human serum albumin.

    abstract::Proalbumins are rare genetic variants of human serum albumin containing a basic propeptide that is not removed during post-transcriptional processing because of a mutation in the site of excision, an Arg-Arg sequence. We have identified the amino acid substitutions in three different types of proalbumins designated Ga...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.21.7403

    authors: Takahashi N,Takahashi Y,Putnam FW

    更新日期:1987-11-01 00:00:00

  • In vivo imaging of calcium accumulation in fly interneurons as elicited by visual motion stimulation.

    abstract::The computation of motion plays a central role in visual orientation. The fly has been successfully used as a model system for analyzing the mechanisms underlying motion detection. Thereby, much attention has been paid to a neuronal circuit of individually identifiable neurons in the third visual ganglion that extract...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.9.4139

    authors: Borst A,Egelhaaf M

    更新日期:1992-05-01 00:00:00

  • Single-molecule visualization of Saccharomyces cerevisiae leading-strand synthesis reveals dynamic interaction between MTC and the replisome.

    abstract::The replisome, the multiprotein system responsible for genome duplication, is a highly dynamic complex displaying a large number of different enzyme activities. Recently, the Saccharomyces cerevisiae minimal replication reaction has been successfully reconstituted in vitro. This provided an opportunity to uncover the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1711291114

    authors: Lewis JS,Spenkelink LM,Schauer GD,Hill FR,Georgescu RE,O'Donnell ME,van Oijen AM

    更新日期:2017-10-03 00:00:00

  • The hemochromatosis protein HFE inhibits iron export from macrophages.

    abstract::Hereditary hemochromatosis (HH) is a disorder of iron metabolism caused by common mutations in the gene HFE. The HFE protein binds to transferrin receptor-1 (TfR1) in competition with transferrin, and in vitro, reduces cellular iron by reducing iron uptake. However, in vivo, HFE is strongly expressed by liver macropha...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.242614699

    authors: Drakesmith H,Sweetland E,Schimanski L,Edwards J,Cowley D,Ashraf M,Bastin J,Townsend AR

    更新日期:2002-11-26 00:00:00

  • Molecular ruler determines needle length for the Salmonella Spi-1 injectisome.

    abstract::The type-III secretion (T3S) systems of bacteria are part of self-assembling nanomachines: the bacterial flagellum that enables cells to propel themselves through liquid and across hydrated surfaces, and the injectisome that delivers pathogenic effector proteins into eukaryotic host cells. Although the flagellum and i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1423492112

    authors: Wee DH,Hughes KT

    更新日期:2015-03-31 00:00:00

  • Lysinuric protein intolerance mutation is expressed in the plasma membrane of cultured skin fibroblasts.

    abstract::Lysinuric protein intolerance (LPI) is an autosomal recessive phenotype consistent with impaired transport of cationic amino acids at the basolateral membrane of intestinal and renal epithelia. On the assumption that the basolateral membrane of epithelial cells and plasma membrane of parenchymal cells are functional a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.21.7711

    authors: Smith DW,Scriver CR,Tenenhouse HS,Simell O

    更新日期:1987-11-01 00:00:00

  • Nucleotide sequence of the 3' region of an infectious human T-cell leukemia virus type II genome.

    abstract::The nucleic acid sequence of the 3' region of human T-cell leukemia virus type II (HTLV-II) proviral DNA was determined using a HTLV-II proviral clone that could be recovered as infectious, transforming virus. The sequence data indicate a region of unknown function of approximately equal to 1.6 kilobase pairs in the 3...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.21.6657

    authors: Shimotohno K,Wachsman W,Takahashi Y,Golde DW,Miwa M,Sugimura T,Chen IS

    更新日期:1984-11-01 00:00:00

  • Pyrophosphate inhibition of rho ATPase: a mechanism of coupling to RNA polymerase activity.

    abstract::The effects of pyrophosphate on RNA binding and ATPase activities of Escherichia coli transcription termination factor rho have been studied. Mutant rho-115 protein has a temperature-sensitive RNA-dependent ATPase activity due to the thermolability of binding to RNA [Kent, R.B. & Guterman, S.K. (1981) Fed. Proc. Fed. ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.13.3992

    authors: Kent RB,Guterman SK

    更新日期:1982-07-01 00:00:00

  • The changing carbon cycle at Mauna Loa Observatory.

    abstract::The amplitude of the CO(2) seasonal cycle at the Mauna Loa Observatory (MLO) increased from the early 1970s to the early 1990s but decreased thereafter despite continued warming over northern continents. Because of its location relative to the large-scale atmospheric circulation, the MLO receives mainly Eurasian air m...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0611224104

    authors: Buermann W,Lintner BR,Koven CD,Angert A,Pinzon JE,Tucker CJ,Fung IY

    更新日期:2007-03-13 00:00:00

  • In vivo imaging of lymphatic vessels in development, wound healing, inflammation, and tumor metastasis.

    abstract::Lymphatic vessel growth or lymphangiogenesis occurs during embryonic development and wound healing and plays an important role in tumor metastasis and inflammatory diseases. However, the possibility of noninvasive detection and quantification of lymphangiogenesis has been lacking. Here, we present the Vegfr3(EGFPLuc) ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1115542109

    authors: Martínez-Corral I,Olmeda D,Diéguez-Hurtado R,Tammela T,Alitalo K,Ortega S

    更新日期:2012-04-17 00:00:00

  • Monolayer purification: a rapid method for isolating protein complexes for single-particle electron microscopy.

    abstract::Visualizing macromolecular complexes by single-particle electron microscopy (EM) entails stringent biochemical purification, specimen preparation, low-dose imaging, and 3D image reconstruction. Here, we introduce the "monolayer purification" method, which employs nickel-nitrilotriacetic acid (Ni-NTA) functionalized li...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0800867105

    authors: Kelly DF,Dukovski D,Walz T

    更新日期:2008-03-25 00:00:00

  • Transferrin-polycation conjugates as carriers for DNA uptake into cells.

    abstract::We have developed a high-efficiency nucleic acid delivery system that uses receptor-mediated endocytosis to carry DNA macromolecules into cells. We accomplished this by conjugating the iron-transport protein transferrin to polycations that bind nucleic acids. Human transferrin, as well as the chicken homologue conalbu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.9.3410

    authors: Wagner E,Zenke M,Cotten M,Beug H,Birnstiel ML

    更新日期:1990-05-01 00:00:00

  • Quantifying changes in the thiol redox proteome upon oxidative stress in vivo.

    abstract::Antimicrobial levels of reactive oxygen species (ROS) are produced by the mammalian host defense to kill invading bacteria and limit bacterial colonization. One main in vivo target of ROS is the thiol group of proteins. We have developed a quantitative thiol trapping technique termed OxICAT to identify physiologically...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0707723105

    authors: Leichert LI,Gehrke F,Gudiseva HV,Blackwell T,Ilbert M,Walker AK,Strahler JR,Andrews PC,Jakob U

    更新日期:2008-06-17 00:00:00

  • Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease.

    abstract::Allergic asthma is an inflammatory disease of the lung characterized by abnormal T helper-2 (T(H)2) lymphocyte responses to inhaled antigens. The molecular mechanisms leading to the generation of T(H)2 responses remain unclear, although toll-like receptors (TLRs) present on innate immune cells play a pivotal role in s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0905063106

    authors: Mattes J,Collison A,Plank M,Phipps S,Foster PS

    更新日期:2009-11-03 00:00:00

  • Measurement and purification of human chromosomes by flow cytometry and sorting.

    abstract::The 24 human chromosome types of normal diploid fibroblast cell strain were classified into 15 groups by high-resolution flow cytometry on the basis of 33258 Hoechst fluorescence. Chromosomes associated with each group were flow sorted onto microscope slides and identified by quinacrine banding analysis. DNA cytophoto...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.3.1382

    authors: Carrano AV,Gray JW,Langlois RG,Burkhart-Schultz KJ,Van Dilla MA

    更新日期:1979-03-01 00:00:00

  • Postischemic PKC activation rescues retrograde and anterograde long-term memory.

    abstract::Therapeutics for cerebral ischemia/hypoxia, which often results in ischemic stroke in humans, are a global unmet medical need. Here, we report that bryostatin-1, a highly potent protein kinase C (PKC) activator, interrupts pathophysiological molecular cascades and apoptosis triggered by cerebral ischemia/hypoxia, enha...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0907842106

    authors: Sun MK,Hongpaisan J,Alkon DL

    更新日期:2009-08-25 00:00:00

  • Secondary PDZ domain-binding site on class B plexins enhances the affinity for PDZ-RhoGEF.

    abstract::PDZ domains are abundant protein interaction modules and typically recognize a short motif at the C terminus of their ligands, with a few residues in the motif endowing the binding specificity. The sequence-based rules, however, cannot fully account for the specificity between the vast number of PDZ domains and ligand...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1508931112

    authors: Pascoe HG,Gutowski S,Chen H,Brautigam CA,Chen Z,Sternweis PC,Zhang X

    更新日期:2015-12-01 00:00:00

  • Purification of replication protein C, a cellular protein involved in the initial stages of simian virus 40 DNA replication in vitro.

    abstract::The replication of simian virus 40 (SV40) DNA is dependent upon a single viral protein [tumor (T) antigen] and multiple cellular proteins. To define the required cellular proteins, we have made use of a cell-free system that supports the replication of plasmid DNA molecules containing the SV40 origin of replication. W...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.10.3584

    authors: Virshup DM,Kelly TJ

    更新日期:1989-05-01 00:00:00

  • Clonal antibodies for core protein of chondroitin sulfate proteoglycan.

    abstract::Antibodies have been prepared to the core protein of cartilage chondroitin sulfate proteoglycan from clones isolated after fusion of rat spleen cells and mouse myeloma cell lines. Antibodies produced by five clones were studied in detail by a radioimmunoassay utilizing 35SO42-labeled hyaluronidase-digested chondroitin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.77.7.3971

    authors: Dorfman A,Hall T,Ho PL,Fitch F

    更新日期:1980-07-01 00:00:00

  • Biphasic regulation by dibutyryl cyclic AMP of tubulin and actin mRNA levels in neuroblastoma cells.

    abstract::Blot hybridization analysis that used labeled tubulin cDNA probes revealed that N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate [dibutyryl cyclic AMP (Bt2cAMP)] initially increases and later decreases the level of tubulin mRNA in a neuroblastoma-glioma hybrid cell line as well as in the parent cells. A significan...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.14.4243

    authors: Ginzburg I,Rybak S,Kimhi Y,Littauer UZ

    更新日期:1983-07-01 00:00:00

  • Mesoscale texture of cement hydrates.

    abstract::Strength and other mechanical properties of cement and concrete rely upon the formation of calcium-silicate-hydrates (C-S-H) during cement hydration. Controlling structure and properties of the C-S-H phase is a challenge, due to the complexity of this hydration product and of the mechanisms that drive its precipitatio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1520487113

    authors: Ioannidou K,Krakowiak KJ,Bauchy M,Hoover CG,Masoero E,Yip S,Ulm FJ,Levitz P,Pellenq RJ,Del Gado E

    更新日期:2016-02-23 00:00:00

  • Functional organization of intrinsic and feedback presynaptic inputs in the primary visual cortex.

    abstract::In the primary visual cortex (V1) of many mammalian species, neurons are spatially organized according to their preferred orientation into a highly ordered map. However, whether and how the various presynaptic inputs to V1 neurons are organized relative to the neuronal orientation map remain unclear. To address this i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1719711115

    authors: Zhang QF,Li H,Chen M,Guo A,Wen Y,Poo MM

    更新日期:2018-05-29 00:00:00

  • Genome-wide RNAi screening identifies protein damage as a regulator of osmoprotective gene expression.

    abstract::The detection, stabilization, and repair of stress-induced damage are essential requirements for cellular life. All cells respond to osmotic stress-induced water loss with increased expression of genes that mediate accumulation of organic osmolytes, solutes that function as chemical chaperones and restore osmotic home...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0602987103

    authors: Lamitina T,Huang CG,Strange K

    更新日期:2006-08-08 00:00:00

  • Innate immune receptor NOD2 mediates LGR5+ intestinal stem cell protection against ROS cytotoxicity via mitophagy stimulation.

    abstract::The nucleotide-binding oligomerization domain-containing protein 2 (NOD2) agonist muramyl dipeptide (MDP), a peptidoglycan motif common to all bacteria, supports leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5)+ intestinal stem cell (ISC) survival through NOD2 activation upon an otherwise lethal oxid...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1902788117

    authors: Levy A,Stedman A,Deutsch E,Donnadieu F,Virgin HW,Sansonetti PJ,Nigro G

    更新日期:2020-01-28 00:00:00

  • Cellular and humoral immune responses to adenoviral vectors containing factor IX gene: tolerization of factor IX and vector antigens allows for long-term expression.

    abstract::Recombinant adenoviruses containing the canine factor IX (FIX) cDNA were directly introduced in the hind leg muscle of mice. We show that (i) in nude mice, high expression (1-5 micrograms/ml in plasma) of FIX protein can be detected for > 300 days; (ii) in contrast, expression of FIX protein was transient (7-10 days) ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.5.1401

    authors: Dai Y,Schwarz EM,Gu D,Zhang WW,Sarvetnick N,Verma IM

    更新日期:1995-02-28 00:00:00

  • The central cytoplasmic loop of the major facilitator superfamily of transport proteins governs efficient membrane insertion.

    abstract::Deletion of 5 residues (Delta5) from the central cytoplasmic loop of the lactose permease of Escherichia coli has no significant effect on expression or activity, whereas Delta12 leads to increased rates of permease turnover after membrane insertion and decreased transport activity, and Delta20 abolishes insertion and...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.140224497

    authors: Weinglass AB,Kaback HR

    更新日期:2000-08-01 00:00:00