Human eIF4E promotes mRNA restructuring by stimulating eIF4A helicase activity.

Abstract:

:Elevated eukaryotic initiation factor 4E (eIF4E) levels frequently occur in a variety of human cancers. Overexpression of eIF4E promotes cellular transformation by selectively increasing the translation of proliferative and prosurvival mRNAs. These mRNAs possess highly structured 5'-UTRs that impede ribosome recruitment and scanning, yet the mechanism for how eIF4E abundance elevates their translation is not easily explained by its cap-binding activity. Here, we show that eIF4E possesses an unexpected second function in translation initiation by strongly stimulating eukaryotic initiation factor 4A (eIF4A) helicase activity. Importantly, we demonstrate that this activity promotes mRNA restructuring in a manner that is independent of its cap-binding function. To explain these findings, we show that the eIF4E-binding site in eukaryotic initiation factor 4G (eIF4G) functions as an autoinhibitory domain to modulate its ability to stimulate eIF4A helicase activity. Binding of eIF4E counteracts this autoinhibition, enabling eIF4G to stimulate eIF4A helicase activity. Finally, we have successfully separated the two functions of eIF4E to show that its helicase promoting activity increases the rate of translation by a mechanism that is distinct from its cap-binding function. Based on our results, we propose that maintaining a connection between eIF4E and eIF4G throughout scanning provides a plausible mechanism to explain how eIF4E abundance selectively stimulates the translation of highly structured proliferation and tumor-promoting mRNAs.

authors

Feoktistova K,Tuvshintogs E,Do A,Fraser CS

doi

10.1073/pnas.1303781110

subject

Has Abstract

pub_date

2013-08-13 00:00:00

pages

13339-44

issue

33

eissn

0027-8424

issn

1091-6490

pii

1303781110

journal_volume

110

pub_type

杂志文章
  • An N-terminal domain of Dbf4p mediates interaction with both origin recognition complex (ORC) and Rad53p and can deregulate late origin firing.

    abstract::The Dbf4Cdc7 kinase acts at the level of individual origins to promote the initiation of DNA replication. We demonstrate through both immunoprecipitation and two-hybrid assays that a domain comprising the first 296 aa of Dbf4p interacts with Orc2p and Orc3p subunits of the origin recognition complex (ORC). Given that ...

    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.252093999

    authors: Duncker BP,Shimada K,Tsai-Pflugfelder M,Pasero P,Gasser SM

    更新日期:2002-12-10 00:00:00

  • Negative regulation of Rb expression by the p53 gene product.

    abstract::Mutation of the p53 gene is one of the most frequent genetic changes found in human cancers. Recent experiments indicated that p53 might contain a transcription-activating domain, which functions when directed to a promoter. This study shows that wild-type p53 suppresses transcription of the retinoblastoma (Rb) gene. ...

    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.89.12.5206

    authors: Shiio Y,Yamamoto T,Yamaguchi N

    更新日期:1992-06-15 00:00:00

  • GDF11 promotes osteogenesis as opposed to MSTN, and follistatin, a MSTN/GDF11 inhibitor, increases muscle mass but weakens bone.

    abstract::Growth and differentiation factor 11 (GDF11) and myostatin (MSTN) are closely related transforming growth factor β (TGF-β) family members, but their biological functions are quite distinct. While MSTN has been widely shown to inhibit muscle growth, GDF11 regulates skeletal patterning and organ development during embry...

    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.1916034117

    authors: Suh J,Kim NK,Lee SH,Eom JH,Lee Y,Park JC,Woo KM,Baek JH,Kim JE,Ryoo HM,Lee SJ,Lee YS

    更新日期:2020-03-03 00:00:00

  • Attributes of an alluvial river and their relation to water policy and management.

    abstract::Rivers around the world are being regulated by dams to accommodate the needs of a rapidly growing global population. These regulatory efforts usually oppose the natural tendency of rivers to flood, move sediment, and migrate. Although an economic benefit, river regulation has come at unforeseen and unevaluated cumulat...

    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.97.22.11858

    authors: Trush WJ,McBain SM,Leopold LB

    更新日期:2000-10-24 00:00:00

  • Localization of myosin-V in the centrosome.

    abstract::The perinuclear localization of myosin-V was investigated in a variety of cultured mammalian cells and in primary cultures of rat hippocampus. In all cells investigated, myosin-V immunoreactivity was associated with the centrosome. In interphase cells, myosin-V was found in pericentriolar material, and in both mother ...

    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.95.15.8636

    authors: Espreafico EM,Coling DE,Tsakraklides V,Krogh K,Wolenski JS,Kalinec G,Kachar B

    更新日期:1998-07-21 00:00:00

  • Role of loop-helix interactions in stabilizing four-helix bundle proteins.

    abstract::One of the critical issues regarding proteins with a four-helix bundle motif is which interactions play the major role in stabilizing this type of folded structure: the interaction among the four alpha-helices or the interaction between the loop and helix segments. To answer this question, an energetic analysis has be...

    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.89.16.7315

    authors: Chou KC,Maggiora GM,Scheraga HA

    更新日期:1992-08-15 00:00:00

  • Temporal dynamics of natural product biosynthesis in marine cyanobacteria.

    abstract::Sessile marine organisms are prolific sources of biologically active natural products. However, these compounds are often found in highly variable amounts, with the abiotic and biotic factors governing their production remaining poorly understood. We present an approach that permits monitoring of in vivo natural produ...

    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.1012813108

    authors: Esquenazi E,Jones AC,Byrum T,Dorrestein PC,Gerwick WH

    更新日期:2011-03-29 00:00:00

  • Behavior of hematopoietic stem cells in a large animal.

    abstract::To study the behavior of hematopoietic stem cells in vivo, we transplanted glucose-6-phosphate dehydrogenase (G6PD) heterozygous (female Safari) cats with small amounts of autologous marrow. The G6PD phenotypes of erythroid burst-forming units and granulocyte/macrophage colony-forming units were repeatedly assayed for...

    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.92.6.2031

    authors: Abkowitz JL,Persik MT,Shelton GH,Ott RL,Kiklevich JV,Catlin SN,Guttorp P

    更新日期:1995-03-14 00:00:00

  • Induction of apoptotic DNA damage and cell death by activation of the sphingomyelin pathway.

    abstract::The potential involvement of ceramide-related signaling processes in the induction of apoptosis by tumor necrosis factor alpha was assessed by multiple biochemical strategies in the human leukemic cell lines HL-60 and U937 and the murine fibrosarcoma cell lines L929/LM and WEHI 164/13. Exposure of these cells to tumor...

    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.91.1.73

    authors: Jarvis WD,Kolesnick RN,Fornari FA,Traylor RS,Gewirtz DA,Grant S

    更新日期:1994-01-04 00:00:00

  • Arabidopsis thaliana transcription factors bZIP19 and bZIP23 regulate the adaptation to zinc deficiency.

    abstract::Zinc is an essential micronutrient for all living organisms. When facing a shortage in zinc supply, plants adapt by enhancing the zinc uptake capacity. The molecular regulators controlling this adaptation are not known. We present the identification of two closely related members of the Arabidopsis thaliana basic-regi...

    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.1004788107

    authors: Assunção AG,Herrero E,Lin YF,Huettel B,Talukdar S,Smaczniak C,Immink RG,van Eldik M,Fiers M,Schat H,Aarts MG

    更新日期:2010-06-01 00:00:00

  • p53 accumulates but is functionally impaired when DNA synthesis is blocked.

    abstract::p53 is required for the induction of a G(1) and/or G(2) irreversible arrest after gamma irradiation (IR), whereas blocked DNA replication causes a p53-independent S-phase arrest. We have examined the response to p53 when DNA synthesis is blocked by hydroxyurea (HU) or aphidicolin or when DNA is damaged by gamma IR. Si...

    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.021282898

    authors: Gottifredi V,Shieh S,Taya Y,Prives C

    更新日期:2001-01-30 00:00:00

  • Capturing native long-range contiguity by in situ library construction and optical sequencing.

    abstract::The relatively short read lengths associated with the most cost-effective DNA sequencing technologies have limited their use in de novo genome assembly, structural variation detection, and haplotype-resolved genome sequencing. Consequently, there is a strong need for methods that capture various scales of contiguity 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.1202680109

    authors: Schwartz JJ,Lee C,Hiatt JB,Adey A,Shendure J

    更新日期:2012-11-13 00:00:00

  • Fossil vertebrates from Antigua, Lesser Antilles: Evidence for late Holocene human-caused extinctions in the West Indies.

    abstract::Vertebrate remains recovered from a limestone fissure filling on Antigua, Lesser Antilles, are associated with radiocarbon dates ranging from 4300 to 2500 yr B.P., contemporaneous with the earliest aboriginal human occupation of the island. Nine taxa of lizards, snakes, birds, bats, and rodents (one-third of the total...

    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.81.14.4448

    authors: Steadman DW,Pregill GK,Olson SL

    更新日期:1984-07-01 00:00:00

  • Interferon induction: a conformational hypothesis.

    abstract::The ability of polynucleotides or polynucleotide duplexes such as poly(I).poly(C) to induce interferon production is proposed to depend on the existence of certain stable glycosidic orientations. It appears that a slight increase in instability of 1--3 kcal/mole (1 cal = 4.184 J) in the conformational regions near 20 ...

    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.76.3.1018

    authors: Miles DL,Miles DW,Eyring H

    更新日期:1979-03-01 00:00:00

  • Structure-function analysis of pneumococcal DprA protein reveals that dimerization is crucial for loading RecA recombinase onto DNA during transformation.

    abstract::Transformation promotes genome plasticity in bacteria via RecA-driven homologous recombination. In the gram-positive human pathogen Streptococcus pneumoniae, the transformasome a multiprotein complex, internalizes, protects, and processes transforming DNA to generate chromosomal recombinants. Double-stranded DNA is in...

    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.1205638109

    authors: Quevillon-Cheruel S,Campo N,Mirouze N,Mortier-Barrière I,Brooks MA,Boudes M,Durand D,Soulet AL,Lisboa J,Noirot P,Martin B,van Tilbeurgh H,Noirot-Gros MF,Claverys JP,Polard P

    更新日期:2012-09-11 00:00:00

  • Hippocampal long-term depression is required for the consolidation of spatial memory.

    abstract::Although NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) and long-term depression (LTD) of glutamatergic transmission are candidate mechanisms for long-term spatial memory, the precise contributions of LTP and LTD remain poorly understood. Here, we report that LTP and LTD in the hippocampal CA1 region of ...

    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.1008200107

    authors: Ge Y,Dong Z,Bagot RC,Howland JG,Phillips AG,Wong TP,Wang YT

    更新日期:2010-09-21 00:00:00

  • G9a drives hypoxia-mediated gene repression for breast cancer cell survival and tumorigenesis.

    abstract::G9a is an epigenetic regulator that methylates H3K9, generally causing repression of gene expression, and participates in diverse cellular functions. G9a is genetically deregulated in a variety of tumor types and can silence tumor suppressor genes and, therefore, is important for carcinogenesis. Although hypoxia is re...

    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.1618706114

    authors: Casciello F,Al-Ejeh F,Kelly G,Brennan DJ,Ngiow SF,Young A,Stoll T,Windloch K,Hill MM,Smyth MJ,Gannon F,Lee JS

    更新日期:2017-07-03 00:00:00

  • Parkinson disease: a new link between monoamine oxidase and mitochondrial electron flow.

    abstract::Two factors that contribute to the progression of Parkinson disease are a brain defect in mitochondrial respiration and the generation of hydrogen peroxide (H2O2) by monoamine oxidase (MAO). Here we show that the two are linked. Metabolism of the neurotransmitter dopamine, or other monoamines (benzylamine, tyramine), ...

    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.94.10.4890

    authors: Cohen G,Farooqui R,Kesler N

    更新日期:1997-05-13 00:00:00

  • The autophagic machinery ensures nonlytic transmission of mycobacteria.

    abstract::In contrast to mechanisms mediating uptake of intracellular bacterial pathogens, bacterial egress and cell-to-cell transmission are poorly understood. Previously, we showed that the transmission of pathogenic mycobacteria between phagocytic cells also depends on nonlytic ejection through an F-actin based structure, ca...

    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.1423318112

    authors: Gerstenmaier L,Pilla R,Herrmann L,Herrmann H,Prado M,Villafano GJ,Kolonko M,Reimer R,Soldati T,King JS,Hagedorn M

    更新日期:2015-02-17 00:00:00

  • The antisense bcl-2-IgH transcript is an optimal target for synthetic oligonucleotides.

    abstract::In most human follicular B cell lymphomas the bcl-2 gene is up-regulated as a result of the t(14;18) chromosomal translocation generating a hybrid bcl-2-IgH mRNA. Recently, we have identified in t(14;18)-positive cells a bcl-2-IgH mRNA in the antisense orientation, putatively responsible for the overexpression of bcl-...

    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.94.15.8150

    authors: Morelli S,Delia D,Capaccioli S,Quattrone A,Schiavone N,Bevilacqua A,Tomasini S,Nicolin A

    更新日期:1997-07-22 00:00:00

  • Materials by numbers: computations as tools of discovery.

    abstract::Current issues pertaining to theoretical simulations of materials, with a focus on systems of nanometer-scale dimensions, are discussed. The use of atomistic simulations as high-resolution numerical experiments, enabling and guiding formulation and testing of analytic theoretical descriptions, is demonstrated through ...

    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.0408038102

    authors: Landman U

    更新日期:2005-05-10 00:00:00

  • Obesity and hyperleptinemia in metallothionein (-I and -II) null mice.

    abstract::Metallothionein (MT) has several putative roles in metal detoxification, in Zn and Cu homeostasis, in scavenging free radicals, and in the acute phase response. Mice of mixed 129/Ola and C57BL/6J background with targeted disruption of MT-I and MT-II genes are more sensitive to toxic metals and oxidative stress. We not...

    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.95.1.358

    authors: Beattie JH,Wood AM,Newman AM,Bremner I,Choo KH,Michalska AE,Duncan JS,Trayhurn P

    更新日期:1998-01-06 00:00:00

  • Bves directly interacts with GEFT, and controls cell shape and movement through regulation of Rac1/Cdc42 activity.

    abstract::Bves is an integral membrane protein with no determined function and no homology to proteins outside of the Popdc family. It is widely expressed throughout development in myriad organisms. Here, we demonstrate an interaction between Bves and guanine nucleotide exchange factor T (GEFT), a GEF for Rho-family GTPases. Th...

    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.0802345105

    authors: Smith TK,Hager HA,Francis R,Kilkenny DM,Lo CW,Bader DM

    更新日期:2008-06-17 00:00:00

  • Regulation of heat production in the inflorescences of an Arum lily by endogenous salicylic acid.

    abstract::We have recently purified calorigen, the natural trigger for heat production in the inflorescences of Sauromatum guttatum Schott (voodoo lily), a thermogenic plant, and identified it as salicylic acid. Since then an analytical assay was developed that allows the quantitation of salicylic acid in plant tissues. This as...

    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.86.7.2214

    authors: Raskin I,Turner IM,Melander WR

    更新日期:1989-04-01 00:00:00

  • Lymphospecific toxicity in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency: possible role of nucleoside kinase(s).

    abstract::Inherited deficiencies of the enzymes adenosine deaminase (adenosine aminohydrolase; EC 3.5.4.4) and purine nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase; EC 2.4.2.1) preferentially interfere with lymphocyte development while sparing most other organ systems. Previous experiments have 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.74.12.5677

    authors: Carson DA,Kaye J,Seegmiller JE

    更新日期:1977-12-01 00:00:00

  • Mechanism of spontaneous vesiculation.

    abstract::Both naturally occurring and synthetic phosphatidic acid (PtdOH) molecules show the phenomenon of spontaneous vesiculation on jump in pH value. This method involves a transient increase in pH of smectic PtdOH dispersions to values between 10 and 12. Such a pH increase induces spontaneous vesiculation with the formatio...

    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.86.14.5351

    authors: Hauser H

    更新日期:1989-07-01 00:00:00

  • Terminal attack trajectories of peregrine falcons are described by the proportional navigation guidance law of missiles.

    abstract::The ability to intercept uncooperative targets is key to many diverse flight behaviors, from courtship to predation. Previous research has looked for simple geometric rules describing the attack trajectories of animals, but the underlying feedback laws have remained obscure. Here, we use GPS loggers and onboard video ...

    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.1714532114

    authors: Brighton CH,Thomas ALR,Taylor GK

    更新日期:2017-12-19 00:00:00

  • Identification of an epithelial cell receptor responsible for Clostridium difficile TcdB-induced cytotoxicity.

    abstract::Clostridium difficile is the leading cause of hospital-acquired diarrhea in the United States. The two main virulence factors of C. difficile are the large toxins, TcdA and TcdB, which enter colonic epithelial cells and cause fluid secretion, inflammation, and cell death. Using a gene-trap insertional mutagenesis scre...

    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.1500791112

    authors: LaFrance ME,Farrow MA,Chandrasekaran R,Sheng J,Rubin DH,Lacy DB

    更新日期:2015-06-02 00:00:00

  • Interacting TCP and NLP transcription factors control plant responses to nitrate availability.

    abstract::Plants have evolved adaptive strategies that involve transcriptional networks to cope with and survive environmental challenges. Key transcriptional regulators that mediate responses to environmental fluctuations in nitrate have been identified; however, little is known about how these regulators interact to orchestra...

    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.1615676114

    authors: Guan P,Ripoll JJ,Wang R,Vuong L,Bailey-Steinitz LJ,Ye D,Crawford NM

    更新日期:2017-02-28 00:00:00

  • Ethylene can stimulate Arabidopsis hypocotyl elongation in the light.

    abstract::Ethylene inhibits hypocotyl elongation in etiolated Arabidopsis seedlings. However, when Arabidopsis was grown in the light in the presence of ethylene or its precursor 1-aminocyclopropane-1-carboxylic acid (ACC), a marked induction of hypocotyl elongation occurred. This resulted from an increase in cell expansion rat...

    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.94.6.2756

    authors: Smalle J,Haegman M,Kurepa J,Van Montagu M,Straeten DV

    更新日期:1997-03-18 00:00:00