Ras activity regulates cyclin E degradation by the Fbw7 pathway.

Abstract:

:The Skp1-Cullin1 F-box protein-Fbw7 ubiquitin ligase regulates phosphorylation-dependent cyclin E degradation, and disruption of this pathway is associated with genetic instability and tumorigenesis. Fbw7 is a human tumor suppressor that is targeted for mutation in primary cancers. However, mechanisms other than mutation of Fbw7 may also disrupt cyclin E proteolysis in cancers. We show that oncogenic Ha-Ras activity regulates cyclin E degradation by the Fbw7 pathway. Activated Ras impairs Fbw7-driven cyclin E degradation, and, conversely, inhibition of normal Ras activity decreases cyclin E abundance. Moreover, activation of the mitogen-activated protein kinase pathway is the essential Ras function that inhibits cyclin E turnover, and activated Ha-Ras expression inhibits both the binding of cyclin E to Fbw7 and cyclin E ubiquitination. Last, we found that oncogenic Ras activity potentiates cyclin E-induced genetic instability but only when cyclin E is susceptible to degradation by Fbw7. Thus, we conclude that Ras activity regulates Fbw7-mediated cyclin E proteolysis and suggest that impaired cyclin E proteolysis is a mechanism through which Ras mutations promote tumorigenesis.

authors

Minella AC,Welcker M,Clurman BE

doi

10.1073/pnas.0503677102

keywords:

subject

Has Abstract

pub_date

2005-07-05 00:00:00

pages

9649-54

issue

27

eissn

0027-8424

issn

1091-6490

pii

0503677102

journal_volume

102

pub_type

杂志文章
  • Drought mediates the importance of stochastic community assembly.

    abstract::Historically, the biodiversity and composition of species in a locality was thought to be influenced primarily by deterministic factors. In such cases, species' niches create differential responses to environmental conditions and interspecific interactions, which combine to determine that locality's biodiversity and 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.0704350104

    authors: Chase JM

    更新日期:2007-10-30 00:00:00

  • Linearity of the hemoglobin oxidation bohr effect.

    abstract::The hemoglobin oxidation Bohr effect below pH 7 is essentially proportional to the fraction of hemes oxidized, just as the ligation Bohr effect is proportional to fractional heme ligation. The reported nonlinear proton release during oxidation [(1965) J. Biol. Chem. 240, 3317-3324] is shown to be an artifact resulting...

    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.73.3.800

    authors: Hoffman BM,Bull C

    更新日期:1976-03-01 00:00:00

  • Carboxyfullerenes as neuroprotective agents.

    abstract::Two regioisomers with C3 or D3 symmetry of water-soluble carboxylic acid C60 derivatives, containing three malonic acid groups per molecule, were synthesized and found to be equipotent free radical scavengers in solution as assessed by EPR analysis. Both compounds also inhibited the excitotoxic death of cultured corti...

    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.94.17.9434

    authors: Dugan LL,Turetsky DM,Du C,Lobner D,Wheeler M,Almli CR,Shen CK,Luh TY,Choi DW,Lin TS

    更新日期:1997-08-19 00:00:00

  • A thermodynamic framework for Mg2+ binding to RNA.

    abstract::We present a model describing how Mg(2+) binds and stabilizes specific RNA structures. In this model, RNA stabilization arises from two energetically distinct modes of Mg(2+) binding: diffuse- and site-binding. Diffusely bound Mg(2+) are electrostatically attracted to the strong anionic field around the RNA and are ac...

    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.221234598

    authors: Misra VK,Draper DE

    更新日期:2001-10-23 00:00:00

  • Extracellular vesicle-associated VEGF-C promotes lymphangiogenesis and immune cells infiltration in endometriosis.

    abstract::Endometriosis is a highly prevalent gynecological disease with severe negative impacts on life quality and financial burden. Unfortunately, there is no cure for this disease, which highlights the need for further investigation about the pathophysiology of this disease to provide clues for developing novel therapeutic ...

    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.1920037117

    authors: Li WN,Hsiao KY,Wang CA,Chang N,Hsu PL,Sun CH,Wu SR,Wu MH,Tsai SJ

    更新日期:2020-10-13 00:00:00

  • Anomalous anisotropic compression behavior of superconducting CrAs under high pressure.

    abstract::CrAs was observed to possess the bulk superconductivity under high-pressure conditions. To understand the superconducting mechanism and explore the correlation between the structure and superconductivity, the high-pressure structural evolution of CrAs was investigated using the angle-dispersive X-ray diffraction (XRD)...

    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.1520570112

    authors: Yu Z,Wu W,Hu Q,Zhao J,Li C,Yang K,Cheng J,Luo J,Wang L,Mao HK

    更新日期:2015-12-01 00:00:00

  • A nondefective (competent) adenovirus-SV40 hybrid isolated from the AD.2-SV40 hybrid population.

    abstract::A new nondefective hybrid virus has been plaque-isolated from the Ad.2-SV40 hybrid population. This virus replicates efficiently with one-hit kinetics in both human embryonic kidney and African green monkey kidney cells, induces an SV40 specific antigen which is detectable by immunofluorescence and complement-fixation...

    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.63.4.1128

    authors: Lewis AM Jr,Levin MJ,Wiese WH,Crumpacker CS,Henry PH

    更新日期:1969-08-01 00:00:00

  • Surface attachment induces Pseudomonas aeruginosa virulence.

    abstract::Pseudomonas aeruginosa infects every type of host that has been examined by deploying multiple virulence factors. Previous studies of virulence regulation have largely focused on chemical cues, but P. aeruginosa may also respond to mechanical cues. Using a rapid imaging-based virulence assay, we demonstrate that P. ae...

    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.1415712111

    authors: Siryaporn A,Kuchma SL,O'Toole GA,Gitai Z

    更新日期:2014-11-25 00:00:00

  • Developmental cell death programs license cytotoxic cells to eliminate histocompatible partners.

    abstract::In a primitive chordate model of natural chimerism, one chimeric partner is often eliminated in a process of allogeneic resorption. Here, we identify the cellular framework underlying loss of tolerance to one partner within a natural Botryllus schlosseri chimera. We show that the principal cell type mediating chimeric...

    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.1606276113

    authors: Corey DM,Rosental B,Kowarsky M,Sinha R,Ishizuka KJ,Palmeri KJ,Quake SR,Voskoboynik A,Weissman IL

    更新日期:2016-06-07 00:00:00

  • Scan statistic-based analysis of exome sequencing data identifies FAN1 at 15q13.3 as a susceptibility gene for schizophrenia and autism.

    abstract::We used a family-based cluster detection approach designed to localize significant rare disease-risk variants clusters within a region of interest to systematically search for schizophrenia (SCZ) susceptibility genes within 49 genomic loci previously implicated by de novo copy number variants. Using two independent wh...

    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.1309475110

    authors: Ionita-Laza I,Xu B,Makarov V,Buxbaum JD,Roos JL,Gogos JA,Karayiorgou M

    更新日期:2014-01-07 00:00:00

  • Dichotomous effects of VEGF-A on adipose tissue dysfunction.

    abstract::Obese fat pads are frequently undervascularized and hypoxic, leading to increased fibrosis, inflammation, and ultimately insulin resistance. We hypothesized that VEGF-A-induced stimulation of angiogenesis enables sustained and sufficient oxygen and nutrient exchange during fat mass expansion, thereby improving adipose...

    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.1200447109

    authors: Sun K,Wernstedt Asterholm I,Kusminski CM,Bueno AC,Wang ZV,Pollard JW,Brekken RA,Scherer PE

    更新日期:2012-04-10 00:00:00

  • Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles.

    abstract::The neuropeptide oxytocin has been implicated in the mediation of several forms of affiliative behavior including parental care, grooming, and sex behavior. Here we demonstrate that species from the genus Microtus (voles) selected for differences in social affiliation show contrasting patterns of oxytocin receptor exp...

    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.89.13.5981

    authors: Insel TR,Shapiro LE

    更新日期:1992-07-01 00:00:00

  • Male-specific transcription initiation of the C4-Slp gene in mouse liver follows activation of STAT5.

    abstract::The mouse genes encoding the constitutively expressed complement component C4 and its closely related isoform C4-Slp (sex-limited protein), which is expressed only in male animals of several strains, provide a unique model to study sequence elements and trans-acting factors responsible for androgen responsiveness. Our...

    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.95.15.8750

    authors: Varin-Blank N,Dondi E,Tosi M,Hernandez C,Boucontet L,Gotoh H,Shiroishi T,Moriwaki K,Meo T

    更新日期:1998-07-21 00:00:00

  • Transloading of tumor antigen-derived peptides into antigen-presenting cells.

    abstract::The discovery of a steadily growing number of tumor antigens (TAs) has made generic, cell-free, peptide-based cancer vaccines a possible alternative to cytokine-transfected autologous cellular cancer vaccines. The major drawback of peptide vaccines, however, is the poor immunogenicity of peptides. It is commonly thoug...

    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.94.7.3256

    authors: Buschle M,Schmidt W,Zauner W,Mechtler K,Trska B,Kirlappos H,Birnstiel ML

    更新日期:1997-04-01 00:00:00

  • Modulation of type beta transforming growth factor activity in bone cultures by osteotropic hormones.

    abstract::Type beta transforming growth factor (TGF-beta) activity was found in conditioned medium harvested from fetal rat and neonatal mouse calvariae by using the anchorage-independent growth of normal rat kidney fibroblasts as an indicator system. Calvariae incubated with parathyroid hormone, 1,25-dihydroxyvitamin D3, 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.84.7.2024

    authors: Pfeilschifter J,Mundy GR

    更新日期:1987-04-01 00:00:00

  • Inhibition of the K+ channel KCa3.1 ameliorates T cell-mediated colitis.

    abstract::The calcium-activated K(+) channel KCa3.1 plays an important role in T lymphocyte Ca(2+) signaling by helping to maintain a negative membrane potential, which provides an electrochemical gradient to drive Ca(2+) influx. To assess the role of KCa3.1 channels in lymphocyte activation in vivo, we studied T cell function ...

    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.0910133107

    authors: Di L,Srivastava S,Zhdanova O,Ding Y,Li Z,Wulff H,Lafaille M,Skolnik EY

    更新日期:2010-01-26 00:00:00

  • Conversion of the Amazon rainforest to agriculture results in biotic homogenization of soil bacterial communities.

    abstract::The Amazon rainforest is the Earth's largest reservoir of plant and animal diversity, and it has been subjected to especially high rates of land use change, primarily to cattle pasture. This conversion has had a strongly negative effect on biological diversity, reducing the number of plant and animal species and homog...

    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.1220608110

    authors: Rodrigues JL,Pellizari VH,Mueller R,Baek K,Jesus Eda C,Paula FS,Mirza B,Hamaoui GS Jr,Tsai SM,Feigl B,Tiedje JM,Bohannan BJ,Nüsslein K

    更新日期:2013-01-15 00:00:00

  • Making technological innovation work for sustainable development.

    abstract::This paper presents insights and action proposals to better harness technological innovation for sustainable development. We begin with three key insights from scholarship and practice. First, technological innovation processes do not follow a set sequence but rather emerge from complex adaptive systems involving many...

    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.1525004113

    authors: Anadon LD,Chan G,Harley AG,Matus K,Moon S,Murthy SL,Clark WC

    更新日期:2016-08-30 00:00:00

  • Decentralization for cost-effective conservation.

    abstract::Since 1930, areas of state-managed forest in the central Himalayas of India have increasingly been devolved to management by local communities. This article studies the long-run effects of the devolution on the cost of forest management and on forest conservation. Village council-management costs an order of magnitude...

    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.0810049106

    authors: Somanathan E,Prabhakar R,Mehta BS

    更新日期:2009-03-17 00:00:00

  • Influence of topology on bacterial social interaction.

    abstract::The environmental topology of complex structures is used by Escherichia coli to create traveling waves of high cell density, a prelude to quorum sensing. When cells are grown to a moderate density within a confining microenvironment, these traveling waves of cell density allow the cells to find and collapse into confi...

    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.1935975100

    authors: Park S,Wolanin PM,Yuzbashyan EA,Lin H,Darnton NC,Stock JB,Silberzan P,Austin R

    更新日期:2003-11-25 00:00:00

  • Ribonucleoprotein and protein factors bind to an H-DNA-forming c-myc DNA element: possible regulators of the c-myc gene.

    abstract::We have located a positive, cis-acting DNA sequence element within the 5' flanking DNA of the c-myc gene (-125 base pairs). This DNA sequence element has a large purine-pyrimidine strand asymmetry and can assume the H-DNA conformation. A factor with the properties of a ribonucleoprotein (RNP) interacts with this DNA r...

    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.86.24.9682

    authors: Davis TL,Firulli AB,Kinniburgh AJ

    更新日期:1989-12-01 00:00:00

  • Variation in the polyadenylylation site of bovine prolactin mRNA.

    abstract::The poly(A) site of bovine prolactin (bPRL) mRNA was examined by phased priming of cDNA synthesis with oligodeoxynucleotides of the general sequence d(pT8-N-N'). The existence of multiple poly(A)-adjacent sequences in bPRL mRNA was indicated by the production of specific chain-termination fragments with at least three...

    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.79.2.223

    authors: Sasavage NL,Smith M,Gillam S,Woychik RP,Rottman FM

    更新日期:1982-01-01 00:00:00

  • Deficient Smad7 expression: a putative molecular defect in scleroderma.

    abstract::Scleroderma is a chronic systemic disease that leads to fibrosis of affected organs. Transforming growth factor (TGF) beta has been implicated in the pathogenesis of scleroderma. Smad proteins are signaling transducers downstream from TGF-beta receptors. Three families of Smads have been identified: (i) receptor-regul...

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

    pub_type: 杂志文章,收录出版

    doi:10.1073/pnas.062010399

    authors: Dong C,Zhu S,Wang T,Yoon W,Li Z,Alvarez RJ,ten Dijke P,White B,Wigley FM,Goldschmidt-Clermont PJ

    更新日期:2002-03-19 00:00:00

  • A model for protein synthesis involving the intermediate formation of peptidyl-5S RNA.

    abstract::A model for protein synthesis is proposed in which the donor for the peptide elongation reaction is peptidyl-5S RNA. Space-filling models show that peptide bond formation between peptidyl-5S RNA and aminoacyl-tRNA is eminently feasible from a stereochemical point of view. The peptide is transferred to 5S RNA, while at...

    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.68.10.2357

    authors: Raacke ID

    更新日期:1971-10-01 00:00:00

  • Sulfanyl stabilization of copper-bonded phenoxyls in model complexes and galactose oxidase.

    abstract::Integrating sulfanyl substituents into copper-bonded phenoxyls significantly alters their optical and redox properties and provides insight into the influence of cysteine modification of the tyrosine cofactor in the enzyme galactose oxidase. The model complexes [1(SR2)](+) are class II mixed-valent Cu(II)-phenoxyl-phe...

    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.1109931108

    authors: Verma P,Pratt RC,Storr T,Wasinger EC,Stack TD

    更新日期:2011-11-15 00:00:00

  • Nanoscale morphological evolution of monocrystalline Pt surfaces during cathodic corrosion.

    abstract::This paper studies the cathodic corrosion of a spherical single crystal of platinum in an aqueous alkaline electrolyte, to map out the detailed facet dependence of the corrosion structures forming during this still largely unexplored electrochemical phenomenon. We find that anisotropic corrosion of the platinum electr...

    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.2017086117

    authors: Arulmozhi N,Hersbach TJP,Koper MTM

    更新日期:2020-12-22 00:00:00

  • Cell cycle-dependent regulation of p185neu: a relationship between disruption of this regulation and transformation.

    abstract::Structure and function of p185neu receptor tyrosine kinase were found to be regulated in a cell cycle-dependent manner. In M phase, p185neu is hyperphosphorylated at serine and/or threonine residues. The phosphotyrosine [Tyr(P)] content of p185neu is at its highest level in G0/G1 phase, decreases through S and G2 phas...

    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.92.4.1092

    authors: Kiyokawa N,Yan DH,Brown ME,Hung MC

    更新日期:1995-02-14 00:00:00

  • Human cytomegalovirus gene expression during infection of primary hematopoietic progenitor cells: a model for latency.

    abstract::Human cytomegalovirus (HCMV) resides latently in hematopoietic cells of the bone marrow. Although viral genomes can be found in CD14+ monocytes and CD34+ progenitor cells, the primary reservoir for latent cytomegalovirus is unknown. We analyzed human hematopoietic subpopulations infected in vitro with a recombinant vi...

    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.252630899

    authors: Goodrum FD,Jordan CT,High K,Shenk T

    更新日期:2002-12-10 00:00:00

  • An intermediate complex in the dissociation of aspartate transcarbamylase.

    abstract::The multisubunit enzyme aspartate transcarbamylase consists of six copies of two types of polypeptide chains, catalytic (C) and regulatory (R). A complex formed by the partial dissociation of this enzyme has been isolated. This species, which has the structure C(6)R(4), is a likely intermediate in the stepwise dissoci...

    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.71.4.1351

    authors: Evans DR,Pastra-Landis SC,Lipscomb WN

    更新日期:1974-04-01 00:00:00

  • The making of the Chandra X-Ray Observatory: the project scientist's perspective.

    abstract::The history of the development of the Chandra X-Ray Observatory is reviewed from a personal perspective. This review is necessarily biased and limited by space because it attempts to cover a time span approaching five decades. ...

    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.0913067107

    authors: Weisskopf MC

    更新日期:2010-04-20 00:00:00