Nucleolar localization of a netrin-1 isoform enhances tumor cell proliferation.

Abstract:

:Netrin-1 displays proto-oncogenic activity in several cancers, which is thought to be due to the ability of this secreted cue to stimulate survival when bound to its receptors. We showed that in contrast to full-length, secreted netrin-1, some cancer cells produced a truncated intranuclear form of netrin-1 (ΔN-netrin-1) through an alternative internal promoter. Because of a nucleolar localization signal located in its carboxyl terminus, ΔN-netrin-1 was targeted to the nucleolus, where it interacted with nucleolar proteins, affected nucleolar ultrastructure, and interacted with the promoters of ribosomal genes. Moreover, ΔN-netrin-1 stimulated cell proliferation in vitro and tumor growth in vivo. Thus, some cancer cells produce not only a full-length, secreted form of netrin-1 that promotes cell survival but also a truncated netrin-1 that stimulates cell proliferation, potentially by enhancing ribosome biogenesis.

journal_name

Sci Signal

journal_title

Science signaling

authors

Delloye-Bourgeois C,Goldschneider D,Paradisi A,Therizols G,Belin S,Hacot S,Rosa-Calatrava M,Scoazec JY,Diaz JJ,Bernet A,Mehlen P

doi

10.1126/scisignal.2002456

subject

Has Abstract

pub_date

2012-08-07 00:00:00

pages

ra57

issue

236

eissn

1945-0877

issn

1937-9145

pii

5/236/ra57

journal_volume

5

pub_type

杂志文章
  • SMAC mimetics and RIPK inhibitors as therapeutics for chronic inflammatory diseases.

    abstract::New therapeutic approaches for chronic inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, and psoriasis are needed because current treatments are often suboptimal in terms of both efficacy and the risks of serious adverse events. Inhibitor of apoptosis proteins (IAPs) are E3 ubiquitin liga...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.aax8295

    authors: Jensen S,Seidelin JB,LaCasse EC,Nielsen OH

    更新日期:2020-02-18 00:00:00

  • Drosophila toll pathway: the new model.

    abstract::In Drosophila, recognition of microbe-specific molecules (such as bacterial peptidoglycans) activates serine protease cascades that converge to activate the Toll pathway. Recent data show that the serine protease Grass, which is activated downstream of pattern recognition receptors and was initially thought to be a co...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.252jc1

    authors: Ashok Y

    更新日期:2009-01-06 00:00:00

  • Mechanochemotransduction during cardiomyocyte contraction is mediated by localized nitric oxide signaling.

    abstract::Cardiomyocytes contract against a mechanical load during each heartbeat, and excessive mechanical stress leads to heart diseases. Using a cell-in-gel system that imposes an afterload during cardiomyocyte contraction, we found that nitric oxide synthase (NOS) was involved in transducing mechanical load to alter Ca(2+) ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2005046

    authors: Jian Z,Han H,Zhang T,Puglisi J,Izu LT,Shaw JA,Onofiok E,Erickson JR,Chen YJ,Horvath B,Shimkunas R,Xiao W,Li Y,Pan T,Chan J,Banyasz T,Tardiff JC,Chiamvimonvat N,Bers DM,Lam KS,Chen-Izu Y

    更新日期:2014-03-18 00:00:00

  • Cycles of ubiquitination and deubiquitination critically regulate growth factor-mediated activation of Akt signaling.

    abstract::K63-linked ubiquitination of Akt is a posttranslational modification that plays a critical role in growth factor-mediated membrane recruitment and activation of Akt. Although E3 ligases involved in growth factor-induced ubiquitination of Akt have been defined, the deubiquitinating enzyme (DUB) that triggers deubiquiti...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2003197

    authors: Yang WL,Jin G,Li CF,Jeong YS,Moten A,Xu D,Feng Z,Chen W,Cai Z,Darnay B,Gu W,Lin HK

    更新日期:2013-01-08 00:00:00

  • Acute O2 sensing through HIF2α-dependent expression of atypical cytochrome oxidase subunits in arterial chemoreceptors.

    abstract::Acute cardiorespiratory responses to O2 deficiency are essential for physiological homeostasis. The prototypical acute O2-sensing organ is the carotid body, which contains glomus cells expressing K+ channels whose inhibition by hypoxia leads to transmitter release and activation of nerve fibers terminating in the brai...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aay9452

    authors: Moreno-Domínguez A,Ortega-Sáenz P,Gao L,Colinas O,García-Flores P,Bonilla-Henao V,Aragonés J,Hüttemann M,Grossman LI,Weissmann N,Sommer N,López-Barneo J

    更新日期:2020-01-21 00:00:00

  • Platelets contribute to amyloid-β aggregation in cerebral vessels through integrin αIIbβ3-induced outside-in signaling and clusterin release.

    abstract::Cerebral amyloid angiopathy (CAA) is a vascular dysfunction disorder characterized by deposits of amyloid-β (Aβ) in the walls of cerebral vessels. CAA and Aβ deposition in the brain parenchyma contribute to dementia and Alzheimer's disease (AD). We investigated the contribution of platelets, which accumulate at vascul...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaf6240

    authors: Donner L,Fälker K,Gremer L,Klinker S,Pagani G,Ljungberg LU,Lothmann K,Rizzi F,Schaller M,Gohlke H,Willbold D,Grenegard M,Elvers M

    更新日期:2016-05-24 00:00:00

  • Probing the mutational landscape of regulators of G protein signaling proteins in cancer.

    abstract::The advent of deep-sequencing techniques has revealed that mutations in G protein-coupled receptor (GPCR) signaling pathways in cancer are more prominent than was previously appreciated. An emergent theme is that cancer-associated mutations tend to cause enhanced GPCR pathway activation to favor oncogenicity. Regulato...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aax8620

    authors: DiGiacomo V,Maziarz M,Luebbers A,Norris JM,Laksono P,Garcia-Marcos M

    更新日期:2020-02-04 00:00:00

  • MARK3-mediated phosphorylation of ARHGEF2 couples microtubules to the actin cytoskeleton to establish cell polarity.

    abstract::The PAR-1-MARK pathway controls cell polarity through the phosphorylation of microtubule-associated proteins. Rho-Rac guanine nucleotide exchange factor 2 (ARHGEF2), which activates Ras homolog family member A (RHOA), is anchored to the microtubule network and sequestered in an inhibited state through binding to dynei...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aan3286

    authors: Sandí MJ,Marshall CB,Balan M,Coyaud É,Zhou M,Monson DM,Ishiyama N,Chandrakumar AA,La Rose J,Couzens AL,Gingras AC,Raught B,Xu W,Ikura M,Morrison DK,Rottapel R

    更新日期:2017-10-31 00:00:00

  • TRPM2 functions as a lysosomal Ca2+-release channel in beta cells.

    abstract::TRPM2 is a Ca2+-permeable cation channel that is specifically activated by adenosine diphosphoribose (ADPR). Channel activation in the plasma membrane leads to Ca2+ influx and has been linked to apoptotic mechanisms. The primary agonist, ADPR, is produced both extra- and intracellularly and causes increases in intrace...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2000278

    authors: Lange I,Yamamoto S,Partida-Sanchez S,Mori Y,Fleig A,Penner R

    更新日期:2009-05-19 00:00:00

  • Corticosteroid receptor balance regulates life and death in cardiomyocytes.

    abstract::Mineralocorticoid receptor (MR) antagonists are effective at treating heart failure. In this issue of Science Signaling, Oakley et al. provide new insight into their cardioprotective actions and highlight the importance of the opposing relationship between the MR and the related glucocorticoid receptor (GR) in the res...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.aaw8715

    authors: Chapman KE

    更新日期:2019-04-16 00:00:00

  • Airway relaxation mechanisms and structural basis of osthole for improving lung function in asthma.

    abstract::Overuse of β2-adrenoceptor agonist bronchodilators evokes receptor desensitization, decreased efficacy, and an increased risk of death in asthma patients. Bronchodilators that do not target β2-adrenoceptors represent a critical unmet need for asthma management. Here, we characterize the utility of osthole, a coumarin ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aax0273

    authors: Wang S,Xie Y,Huo YW,Li Y,Abel PW,Jiang H,Zou X,Jiao HZ,Kuang X,Wolff DW,Huang YG,Casale TB,Panettieri RA Jr,Wei T,Cao Z,Tu Y

    更新日期:2020-11-24 00:00:00

  • The role of ciliary trafficking in Hedgehog receptor signaling.

    abstract::Defects in the biogenesis of or transport through primary cilia affect Hedgehog protein signaling, and many Hedgehog pathway components traffic through or accumulate in cilia. The Hedgehog receptor Patched negatively regulates the activity and ciliary accumulation of Smoothened, a seven-transmembrane protein that is e...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaa5622

    authors: Kim J,Hsia EY,Brigui A,Plessis A,Beachy PA,Zheng X

    更新日期:2015-06-02 00:00:00

  • Acetylation goes global: the emergence of acetylation biology.

    abstract::For the first 30 years since its discovery, reversible protein acetylation has been studied and understood almost exclusively in the context of histone modification and gene transcription. With the discovery of non-histone acetylated proteins and acetylation-modifying enzymes in cellular compartments outside the nucle...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.297pe76

    authors: Norris KL,Lee JY,Yao TP

    更新日期:2009-11-17 00:00:00

  • Focus issue: an expanding world for TGF-beta signaling.

    abstract::The complexity of the signaling network that is initiated by members of the transforming growth factor-beta (TGF-beta) superfamily continues to increase. In addition, Smads, which were originally identified as key transducers of TGF-beta signals, are beginning to emerge as players in other TGF-beta-independent process...

    journal_title:Science signaling

    pub_type: 社论

    doi:10.1126/scisignal.146eg8

    authors: Gough NR

    更新日期:2008-11-18 00:00:00

  • STIM2 enhances receptor-stimulated Ca²⁺ signaling by promoting recruitment of STIM1 to the endoplasmic reticulum-plasma membrane junctions.

    abstract::A central component of receptor-evoked Ca(2+) signaling is store-operated Ca(2+) entry (SOCE), which is activated by the assembly of STIM1-Orai1 channels in endoplasmic reticulum (ER) and plasma membrane (PM) (ER-PM) junctions in response to depletion of ER Ca(2+). We report that STIM2 enhances agonist-mediated activa...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2005748

    authors: Ong HL,de Souza LB,Zheng C,Cheng KT,Liu X,Goldsmith CM,Feske S,Ambudkar IS

    更新日期:2015-01-13 00:00:00

  • Discovering relationships between nuclear receptor signaling pathways, genes, and tissues in Transcriptomine.

    abstract::We previously developed a web tool, Transcriptomine, to explore expression profiling data sets involving small-molecule or genetic manipulations of nuclear receptor signaling pathways. We describe advances in biocuration, query interface design, and data visualization that enhance the discovery of uncharacterized biol...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aah6275

    authors: Becnel LB,Ochsner SA,Darlington YF,McOwiti A,Kankanamge WH,Dehart M,Naumov A,McKenna NJ

    更新日期:2017-04-25 00:00:00

  • Visualizing immune system complexity.

    abstract::The European Molecular Biology Organization (EMBO) meeting Visualizing Immune System Complexity, held in January 2009, covered multiple scales, from imaging single molecules to imaging whole animals. In addition to experimental details, there was an emphasis on modeling both for data analysis and as a predictive tool ...

    journal_title:Science signaling

    pub_type:

    doi:10.1126/scisignal.266mr4

    authors: Dustin ML

    更新日期:2009-04-14 00:00:00

  • Do pancreatic β cells "taste" nutrients to secrete insulin?

    abstract::Insulin secretion from pancreatic β cells is controlled by nutrients, hormones, and neurotransmitters. Unlike the latter, which work through classic receptors, glucose and most other nutrients do not interact with membrane receptors but must be metabolized by β cells to induce insulin secretion. Studies have revealed ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2003325

    authors: Henquin JC

    更新日期:2012-08-28 00:00:00

  • Arabidopsis ATXR2 deposits H3K36me3 at the promoters of LBD genes to facilitate cellular dedifferentiation.

    abstract::Cellular dedifferentiation, the transition of differentiated somatic cells to pluripotent stem cells, ensures developmental plasticity and contributes to wound healing in plants. Wounding induces cells to form a mass of unorganized pluripotent cells called callus at the wound site. Explanted cells can also form callus...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aan0316

    authors: Lee K,Park OS,Seo PJ

    更新日期:2017-11-28 00:00:00

  • Educated natural killer cells show dynamic movement of the activating receptor NKp46 and confinement of the inhibitory receptor Ly49A.

    abstract::Educated natural killer (NK) cells have inhibitory receptors specific for self major histocompatibility complex (MHC) class I molecules and kill cancer cells more efficiently than do NK cells that do not have such receptors (hyporesponsive NK cells). The mechanism behind this functional empowerment through education h...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aai9200

    authors: Staaf E,Hedde PN,Bagawath Singh S,Piguet J,Gratton E,Johansson S

    更新日期:2018-02-13 00:00:00

  • mGluR5 antagonism increases autophagy and prevents disease progression in the zQ175 mouse model of Huntington's disease.

    abstract::Huntington's disease (HD) is a neurodegenerative disease caused by an expansion in the huntingtin protein (also called Htt) that induces neuronal cell death with age. We found that the treatment of 12-month-old symptomatic heterozygous and homozygous zQ175 huntingtin knockin mice for 12 weeks with CTEP, a negative all...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aan6387

    authors: Abd-Elrahman KS,Hamilton A,Hutchinson SR,Liu F,Russell RC,Ferguson SSG

    更新日期:2017-12-19 00:00:00

  • Target acquired: Selective autophagy in cardiometabolic disease.

    abstract::The accumulation of damaged or excess proteins and organelles is a defining feature of metabolic disease in nearly every tissue. Thus, a central challenge in maintaining metabolic homeostasis is the identification, sequestration, and degradation of these cellular components, including protein aggregates, mitochondria,...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.aag2298

    authors: Evans TD,Sergin I,Zhang X,Razani B

    更新日期:2017-02-28 00:00:00

  • The pseudokinase MLKL activates PAD4-dependent NET formation in necroptotic neutrophils.

    abstract::Neutrophil extracellular trap (NET) formation can generate short-term, functional anucleate cytoplasts and trigger loss of cell viability. We demonstrated that the necroptotic cell death effector mixed lineage kinase domain-like (MLKL) translocated from the cytoplasm to the plasma membrane and stimulated downstream NA...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aao1716

    authors: D'Cruz AA,Speir M,Bliss-Moreau M,Dietrich S,Wang S,Chen AA,Gavillet M,Al-Obeidi A,Lawlor KE,Vince JE,Kelliher MA,Hakem R,Pasparakis M,Williams DA,Ericsson M,Croker BA

    更新日期:2018-09-04 00:00:00

  • Real-time dynamics of peptide ligand-dependent receptor complex formation in planta.

    abstract::The CLAVATA (CLV) and flagellin (flg) signaling pathways act through peptide ligands and closely related plasma membrane-localized receptor-like kinases (RLKs). The plant peptide CLV3 regulates stem cell homeostasis, whereas the bacterial flg22 peptide elicits defense responses. We applied multiparameter fluorescence ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aab0598

    authors: Somssich M,Ma Q,Weidtkamp-Peters S,Stahl Y,Felekyan S,Bleckmann A,Seidel CA,Simon R

    更新日期:2015-08-04 00:00:00

  • New connections: New targets for fighting hepatic steatosis.

    abstract::Insight into the signaling pathways that regulate de novo lipogenesis may lead to new treatments for hepatic steatosis. ...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.aam9988

    authors: Wong W

    更新日期:2017-02-21 00:00:00

  • Vemurafenib potently induces endoplasmic reticulum stress-mediated apoptosis in BRAFV600E melanoma cells.

    abstract::The V600E mutation in the kinase BRAF is frequently detected in melanomas and results in constitutive activation of BRAF, which then promotes cell proliferation by the mitogen-activated protein kinase signaling pathway. Although the BRAFV600E kinase inhibitor vemurafenib has remarkable antitumor activity in patients w...

    journal_title:Science signaling

    pub_type: 临床试验,杂志文章

    doi:10.1126/scisignal.2003057

    authors: Beck D,Niessner H,Smalley KS,Flaherty K,Paraiso KH,Busch C,Sinnberg T,Vasseur S,Iovanna JL,Drießen S,Stork B,Wesselborg S,Schaller M,Biedermann T,Bauer J,Lasithiotakis K,Weide B,Eberle J,Schittek B,Schadendorf D,G

    更新日期:2013-01-29 00:00:00

  • Differential regulation of Ca2+ influx by ORAI channels mediates enamel mineralization.

    abstract::Store-operated Ca2+ entry (SOCE) channels are highly selective Ca2+ channels activated by the endoplasmic reticulum (ER) sensors STIM1 and STIM2. Their direct interaction with the pore-forming plasma membrane ORAI proteins (ORAI1, ORAI2, and ORAI3) leads to sustained Ca2+ fluxes that are critical for many cellular fun...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aav4663

    authors: Eckstein M,Vaeth M,Aulestia FJ,Costiniti V,Kassam SN,Bromage TG,Pedersen P,Issekutz T,Idaghdour Y,Moursi AM,Feske S,Lacruz RS

    更新日期:2019-04-23 00:00:00

  • The adaptor protein insulin receptor substrate 2 inhibits alternative macrophage activation and allergic lung inflammation.

    abstract::Insulin receptor substrate 2 (IRS2) is an adaptor protein that becomes tyrosine-phosphorylated in response to the cytokines interleukin-4 (IL-4) and IL-13, which results in activation of the phosphoinositide 3-kinase (PI3K)-Akt pathway. IL-4 and IL-13 contribute to allergic lung inflammation. To examine the role of IR...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aad6724

    authors: Dasgupta P,Dorsey NJ,Li J,Qi X,Smith EP,Yamaji-Kegan K,Keegan AD

    更新日期:2016-06-21 00:00:00

  • Dynamic palmitoylation controls the microdomain localization of the DKK1 receptors CKAP4 and LRP6.

    abstract::Dickkopf1 (DKK1) was originally identified as an antagonist of Wnt signaling that binds to and induces the clathrin-mediated endocytosis of the Wnt coreceptors low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6). DKK1 also binds to cytoskeleton-associated protein 4 (CKAP4), which was originally identifi...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aat9519

    authors: Sada R,Kimura H,Fukata Y,Fukata M,Yamamoto H,Kikuchi A

    更新日期:2019-11-19 00:00:00

  • The E3 ligase RNF43 inhibits Wnt signaling downstream of mutated β-catenin by sequestering TCF4 to the nuclear membrane.

    abstract::Given its fundamental role in development and cancer, the Wnt-β-catenin signaling pathway is tightly controlled at multiple levels. RING finger protein 43 (RNF43) is an E3 ubiquitin ligase originally found in stem cells and proposed to inhibit Wnt signaling by interacting with the Wnt receptors of the Frizzled family....

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aac6757

    authors: Loregger A,Grandl M,Mejías-Luque R,Allgäuer M,Degenhart K,Haselmann V,Oikonomou C,Hatzis P,Janssen KP,Nitsche U,Gradl D,van den Broek O,Destree O,Ulm K,Neumaier M,Kalali B,Jung A,Varela I,Schmid RM,Rad R,Busch DH

    更新日期:2015-09-08 00:00:00