Combined deficiency for MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2) delays tumor development.

Abstract:

:MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2) are protein-serine/threonine kinases that are activated by ERK or p38 and phosphorylate eIF4E, which is involved in cap-dependent translation initiation. However, Mnk1/2 double knockout (Mnk-DKO) mice show normal cell growth and development despite an absence of eIF4E phosphorylation. Here we show that the tumorigenesis occurring in the Lck-Pten mouse model (referred to here as tPten(-/-) mice) can be suppressed by the loss of Mnk1/2. Phosphorylation of eIF4E was greatly enhanced in lymphomas of parental tPten(-/-) mice compared with lymphoid tissues of wild-type mice, but was totally absent in lymphomas of tPten(-/-); Mnk-DKO mice. Notably, stable knockdown of Mnk1 in the human glioma cell line U87MG resulted in dramatically decreased tumor formation when these cells were injected into athymic nude mice. Our data demonstrate an oncogenic role for Mnk1/2 in tumor development, and highlight these molecules as potential anticancer drug targets that could be inactivated with minimal side effects.

authors

Ueda T,Sasaki M,Elia AJ,Chio II,Hamada K,Fukunaga R,Mak TW

doi

10.1073/pnas.1008136107

subject

Has Abstract

pub_date

2010-08-10 00:00:00

pages

13984-90

issue

32

eissn

0027-8424

issn

1091-6490

pii

1008136107

journal_volume

107

pub_type

杂志文章
  • Restoration of fragmentary Babylonian texts using recurrent neural networks.

    abstract::The main sources of information regarding ancient Mesopotamian history and culture are clay cuneiform tablets. Many of these tablets are damaged, leading to missing information. Currently, the missing text is manually reconstructed by experts. We investigate the possibility of assisting scholars, by modeling the langu...

    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.2003794117

    authors: Fetaya E,Lifshitz Y,Aaron E,Gordin S

    更新日期:2020-09-15 00:00:00

  • Proteomic identification of phosphatidylinositol (3,4,5) triphosphate-binding proteins in Dictyostelium discoideum.

    abstract::Phosphatidylinositol (3,4,5)-triphosphate (PtdInsP(3)) mediates intracellular signaling for directional sensing and pseudopod extension at the leading edge of migrating cells during chemotaxis. How this PtdInsP(3) signal is translated into remodeling of the actin cytoskeleton is poorly understood. Here, using a proteo...

    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.1006153107

    authors: Zhang P,Wang Y,Sesaki H,Iijima M

    更新日期:2010-06-29 00:00:00

  • U94 of human herpesvirus 6 is expressed in latently infected peripheral blood mononuclear cells and blocks viral gene expression in transformed lymphocytes in culture.

    abstract::Human herpesvirus 6 (HHV-6) like other herpesviruses, expresses sequentially immediate early (IE), early, and late genes during lytic infection. Evidence of ability to establish latent infection has not been available, but by analogy with other herpesviruses it could be expected that IE genes that regulate and transac...

    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.95.23.13911

    authors: Rotola A,Ravaioli T,Gonelli A,Dewhurst S,Cassai E,Di Luca D

    更新日期:1998-11-10 00:00:00

  • Hsp104 disaggregase at normal levels cures many [PSI+] prion variants in a process promoted by Sti1p, Hsp90, and Sis1p.

    abstract::Overproduction or deficiency of many chaperones and other cellular components cure the yeast prions [PSI+] (formed by Sup35p) or [URE3] (based on Ure2p). However, at normal expression levels, Btn2p and Cur1p eliminate most newly arising [URE3] variants but do not cure [PSI+], even after overexpression. Deficiency or o...

    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.1704016114

    authors: Gorkovskiy A,Reidy M,Masison DC,Wickner RB

    更新日期:2017-05-23 00:00:00

  • Proteins with H-bond packing defects are highly interactive with lipid bilayers: Implications for amyloidogenesis.

    abstract::We noticed that disease-related amyloidogenic proteins and especially cellular prion proteins have the highest proportion of incompletely desolvated backbone H bonds among soluble proteins. Such bonds are vulnerable to water attack and thus represent structural weaknesses. We have measured the adsorption of proteins o...

    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.0335642100

    authors: Fernández A,Berry RS

    更新日期:2003-03-04 00:00:00

  • Chemical and structural analysis of a photoactive vertebrate cryptochrome from pigeon.

    abstract::Computational and biochemical studies implicate the blue-light sensor cryptochrome (CRY) as an endogenous light-dependent magnetosensor enabling migratory birds to navigate using the Earth's magnetic field. Validation of such a mechanism has been hampered by the absence of structures of vertebrate CRYs that have funct...

    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.1907875116

    authors: Zoltowski BD,Chelliah Y,Wickramaratne A,Jarocha L,Karki N,Xu W,Mouritsen H,Hore PJ,Hibbs RE,Green CB,Takahashi JS

    更新日期:2019-09-24 00:00:00

  • Intramembrane charge movements and excitation- contraction coupling expressed by two-domain fragments of the Ca2+ channel.

    abstract::To investigate the molecular basis of the voltage sensor that triggers excitation-contraction (EC) coupling, the four-domain pore subunit of the dihydropyridine receptor (DHPR) was cut in the cytoplasmic linker between domains II and III. cDNAs for the I-II domain (alpha1S 1-670) and the III-IV domain (alpha1S 701-187...

    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.111001898

    authors: Ahern CA,Arikkath J,Vallejo P,Gurnett CA,Powers PA,Campbell KP,Coronado R

    更新日期:2001-06-05 00:00:00

  • Fatty acid-requiring mutant of Saccharomyces cerevisiae defective in acetyl-CoA carboxylase.

    abstract::The isolation and biochemical properties of a Saccharomyces cerevisiae mutant (acc1-167) defective in acetyl-CoA carboxylase [acetyl-CoA:carbon-dioxide ligase (ADP forming), EC 6.4.1.2] activity are described. The mutant is deficient in de novo biosynthesis of long-chain fatty acids and specifically requires a saturat...

    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.77.4.1814

    authors: Roggenkamp R,Numa S,Schweizer E

    更新日期:1980-04-01 00:00:00

  • Identification of cation-binding sites on actin that drive polymerization and modulate bending stiffness.

    abstract::The assembly of actin monomers into filaments and networks plays vital roles throughout eukaryotic biology, including intracellular transport, cell motility, cell division, determining cellular shape, and providing cells with mechanical strength. The regulation of actin assembly and modulation of filament mechanical p...

    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.1211078109

    authors: Kang H,Bradley MJ,McCullough BR,Pierre A,Grintsevich EE,Reisler E,De La Cruz EM

    更新日期:2012-10-16 00:00:00

  • Crystal structure of the homo-tetrameric DNA binding domain of Escherichia coli single-stranded DNA-binding protein determined by multiwavelength x-ray diffraction on the selenomethionyl protein at 2.9-A resolution.

    abstract::The crystal structure of the tetrameric DNA-binding domain of the single-stranded DNA binding protein from Escherichia coli was determined at a resolution of 2.9 A using multiwavelength anomalous dispersion. Each monomer in the tetramer is topologically similar to an oligomer-binding fold. Two monomers each contribute...

    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.94.13.6652

    authors: Raghunathan S,Ricard CS,Lohman TM,Waksman G

    更新日期:1997-06-24 00:00:00

  • Type II regulatory subunits are not required for the anchoring-dependent modulation of Ca2+ channel activity by cAMP-dependent protein kinase.

    abstract::Preferential phosphorylation of specific proteins by cAMP-dependent protein kinase (PKA) may be mediated in part by the anchoring of PKA to a family of A-kinase anchor proteins (AKAPs) positioned in close proximity to target proteins. This interaction is thought to depend on binding of the type II regulatory (RII) sub...

    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.94.20.11067

    authors: Burton KA,Johnson BD,Hausken ZE,Westenbroek RE,Idzerda RL,Scheuer T,Scott JD,Catterall WA,McKnight GS

    更新日期:1997-09-30 00:00:00

  • Targeted ablation of the 25-hydroxyvitamin D 1alpha -hydroxylase enzyme: evidence for skeletal, reproductive, and immune dysfunction.

    abstract::The active form of vitamin D, 1alpha,25-dihydroxyvitamin D [1alpha,25(OH)2D], is synthesized from its precursor 25 hydroxyvitamin D [25(OH)D] via the catalytic action of the 25(OH)D-1alpha-hydroxylase [1alpha(OH)ase] enzyme. Many roles in cell growth and differentiation have been attributed to 1,25(OH)2D, including 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.131029498

    authors: Panda DK,Miao D,Tremblay ML,Sirois J,Farookhi R,Hendy GN,Goltzman D

    更新日期:2001-06-19 00:00:00

  • A localized differentiation-inducing-factor sink in the front of the Dictyostelium slug.

    abstract::Differentiation-inducing factor 1 [DIF-1; 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)-hexan-1-one] induces stalk cell differentiation during Dictyostelium development. It is present as a gradient in the multicellular slug, its lowest concentration being in the anterior. Here we demonstrate the existence of a locali...

    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.90.2.487

    authors: Kay RR,Large S,Traynor D,Nayler O

    更新日期:1993-01-15 00:00:00

  • The novel PII-interactor PirC identifies phosphoglycerate mutase as key control point of carbon storage metabolism in cyanobacteria.

    abstract::Nitrogen limitation imposes a major transition in the lifestyle of nondiazotrophic cyanobacteria that is controlled by a complex interplay of regulatory factors involving the pervasive signal processor PII Immediately upon nitrogen limitation, newly fixed carbon is redirected toward glycogen synthesis. How the metabol...

    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.2019988118

    authors: Orthwein T,Scholl J,Spät P,Lucius S,Koch M,Macek B,Hagemann M,Forchhammer K

    更新日期:2021-02-09 00:00:00

  • An unexpected requirement for brain-type sodium channels for control of heart rate in the mouse sinoatrial node.

    abstract::Voltage-gated Na(+) channels are composed of pore-forming alpha and auxiliary beta subunits. The majority of Na(+) channels in the heart contain tetrodotoxin (TTX)-insensitive Na(v)1.5 alpha subunits, but TTX-sensitive brain-type Na(+) channel alpha subunits are present and functionally important in the transverse tub...

    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.2627986100

    authors: Maier SK,Westenbroek RE,Yamanushi TT,Dobrzynski H,Boyett MR,Catterall WA,Scheuer T

    更新日期:2003-03-18 00:00:00

  • A soluble domain of the membrane-anchoring chain of influenza virus hemagglutinin (HA2) folds in Escherichia coli into the low-pH-induced conformation.

    abstract::The extensive refolding of the membrane-anchoring chain of hemagglutinin (HA) of influenza virus (termed HA2) in cellular endosomes, which initiates viral entry by membrane fusion, suggests that viral HA is meta-stable. HA2 polypeptide residues 38-175 expressed in Escherichia coli are reported here to fold in vivo int...

    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.92.26.12205

    authors: Chen J,Wharton SA,Weissenhorn W,Calder LJ,Hughson FM,Skehel JJ,Wiley DC

    更新日期:1995-12-19 00:00:00

  • Specific regulation by steroid hormones of the amount of type I cyclic AMP-dependent protein kinase holoenzyme.

    abstract::The total amounts of type I and type II cytoplasmic cyclic AMP-dependent protein kinase activities were measured in various tissues of intact rats and rats subjected to castration, hypophysectomy, or adrenalectomy. After castration, the total amount of type I activity decreased rapidly in classifically steroid-respons...

    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.75.1.223

    authors: Fuller DJ,Byus CV,Russell DH

    更新日期:1978-01-01 00:00:00

  • Delivery of foreign antigens by engineered outer membrane vesicle vaccines.

    abstract::As new disease threats arise and existing pathogens grow resistant to conventional interventions, attention increasingly focuses on the development of vaccines to induce protective immune responses. Given their admirable safety records, protein subunit vaccines are attractive for widespread immunization, but their dis...

    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.0805532107

    authors: Chen DJ,Osterrieder N,Metzger SM,Buckles E,Doody AM,DeLisa MP,Putnam D

    更新日期:2010-02-16 00:00:00

  • Pseudomonas cytochrome c551 at 2.0 A resolution: enlargement of the cytochrome c family.

    abstract::The structure of respiratory cytochrome c551 of Pseudomonas aeruginosa, with 82 amino acids, has been solved by x-ray analysis and refined to a crystallographic R factor of 16.2%. It has the same basic folding pattern and hydrophobic heme environment as cytochromes c, c2, and c550, except for a large deletion at the b...

    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.75.6.2674

    authors: Almassy RJ,Dickerson RE

    更新日期:1978-06-01 00:00:00

  • Overcoming design and development challenges in agent-based modeling using ASCAPE.

    abstract::The ASCAPE agent-based modeling environment greatly eases the task of designing and investigating agent-based models. However, effective design can still require a relatively deep knowledge of programming and agent-based modeling. This issue has almost certainly slowed the adoption of agent-based modeling approaches t...

    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.082081199

    authors: Inchiosa ME,Parker MT

    更新日期:2002-05-14 00:00:00

  • Heteromerization of PIP aquaporins affects their intrinsic permeability.

    abstract::The plant aquaporin plasma membrane intrinsic proteins (PIP) subfamily represents one of the main gateways for water exchange at the plasma membrane (PM). A fraction of this subfamily, known as PIP1, does not reach the PM unless they are coexpressed with a PIP2 aquaporin. Although ubiquitous and abundantly expressed, ...

    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.1316537111

    authors: Yaneff A,Sigaut L,Marquez M,Alleva K,Pietrasanta LI,Amodeo G

    更新日期:2014-01-07 00:00:00

  • Nerve growth factor stimulates protein tyrosine phosphorylation in PC-12 pheochromocytoma cells.

    abstract::The cellular actions of nerve growth factor (NGF) and epidermal growth factor (EGF) may be mediated by changes in protein phosphorylation. The tyrosine phosphorylation of two predominant proteins of molecular mass 40 and 42 kDa is seen in PC-12 cells treated with NGF or EGF, correlating with activation of a previously...

    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.88.7.2653

    authors: Miyasaka T,Sternberg DW,Miyasaka J,Sherline P,Saltiel AR

    更新日期:1991-04-01 00:00:00

  • Fast synaptic transmission between striatal spiny projection neurons.

    abstract::Striatal inhibition plays an important role in models of cortex-basal ganglia function and is altered in many basal ganglia diseases. The gamma-aminobutyric acid ergic spiny projection neuron comprises >95% of striatal neurons, but despite strong anatomical evidence, the electrophysiological properties and functions o...

    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.242428599

    authors: Czubayko U,Plenz D

    更新日期:2002-11-26 00:00:00

  • Evidence of tectorial membrane radial motion in a propagating mode of a complex cochlear model.

    abstract::Knowledge of vibratory patterns in the cochlea is crucial to understanding the stimulation of mechanosensory cells. Experiments to determine the motion of the cochlear partition and surrounding fluid are extremely challenging. As a result, the motion data are incomplete and often contradictory. The bending mechanism o...

    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.0401395101

    authors: Cai H,Shoelson B,Chadwick RS

    更新日期:2004-04-20 00:00:00

  • In colorectal cancer mast cells contribute to systemic regulatory T-cell dysfunction.

    abstract::T-regulatory cells (Treg) and mast cells (MC) are abundant in colorectal cancer (CRC) tumors. Interaction between the two is known to promote immune suppression or loss of Treg functions and autoimmunity. Here, we demonstrate that in both human CRC and murine polyposis the outcome of this interaction is the generation...

    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.0913683107

    authors: Blatner NR,Bonertz A,Beckhove P,Cheon EC,Krantz SB,Strouch M,Weitz J,Koch M,Halverson AL,Bentrem DJ,Khazaie K

    更新日期:2010-04-06 00:00:00

  • Monoclonal antibodies against myofibrillar components of rat skeletal muscle decorate the intermediate filaments of cultured cells.

    abstract::Monospecific antibodies were produced in vitro by fusing mouse myeloma cells with spleen cells from a BALB/c mouse immunized with rat skeletal myofibrils. After cloning 3 times on agarose, two stable clones were obtained and chosen for further characterization. The first clone, JLB1, produced an antibody that recogniz...

    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.78.4.2335

    authors: Lin JJ

    更新日期:1981-04-01 00:00:00

  • Decadal predictability without ocean dynamics.

    abstract::This paper shows that the most predictable components of internal variability in coupled atmosphere-ocean models are remarkably similar to the most predictable components of climate models without interactive ocean dynamics (i.e., models whose ocean is represented by a 50-m-deep slab ocean mixed layer with no interact...

    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.1614085114

    authors: Srivastava A,DelSole T

    更新日期:2017-02-28 00:00:00

  • Ubiquitin-conjugating enzyme Ubc13 controls breast cancer metastasis through a TAK1-p38 MAP kinase cascade.

    abstract::Metastatic spread is the leading cause of cancer mortality. Breast cancer (BCa) metastatic recurrence can happen years after removal of the primary tumor. Here we show that Ubc13, an E2 enzyme that catalyzes K63-linked protein polyubiquitination, is largely dispensable for primary mammary tumor growth but is required ...

    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.1414358111

    authors: Wu X,Zhang W,Font-Burgada J,Palmer T,Hamil AS,Biswas SK,Poidinger M,Borcherding N,Xie Q,Ellies LG,Lytle NK,Wu LW,Fox RG,Yang J,Dowdy SF,Reya T,Karin M

    更新日期:2014-09-23 00:00:00

  • The p53-dependent effects of macrophage migration inhibitory factor revealed by gene targeting.

    abstract::Macrophage migration inhibitory factor (MIF) is a mediator of host immunity and functions as a high, upstream activator of cells within the innate and the adaptive immunological systems. Recent studies have suggested a potentially broader role for MIF in growth regulation because of its ability to antagonize p53-media...

    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.1533295100

    authors: Fingerle-Rowson G,Petrenko O,Metz CN,Forsthuber TG,Mitchell R,Huss R,Moll U,Müller W,Bucala R

    更新日期:2003-08-05 00:00:00

  • Docosahexaenoic acid is a strong inhibitor of prostaglandin but not leukotriene biosynthesis.

    abstract::Docosahexaenoic acid (DCHA), a major polyunsaturated acid component of fish lipid, is not a substrate for prostaglandin synthetase from ram seminal vesicles but is a strong competitive inhibitor (Ki, 0.36 microM) of the conversion by this enzyme of arachidonate (Km, 5.9 microM) to prostaglandins. In contrast, DCHA exh...

    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.80.12.3581

    authors: Corey EJ,Shih C,Cashman JR

    更新日期:1983-06-01 00:00:00