Evidence map›Paper›PMID 25187540›Full record

ArticleJournal of virology2014

Mitogen-activated protein kinase-interacting kinase regulates mTOR/AKT signaling and controls the serine/arginine-rich protein kinase-responsive type 1 internal ribosome entry site-mediated translation and viral oncolysis.

Michael C Brown, Mikhail I Dobrikov, Matthias Gromeier

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 40 citations in OpenAlex.

  1. Polio virotherapy provokes MDA5 signaling and CD4Microbiology and molecular biology reviews : MMBR · 2025
    Review
  2. Article
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  4. Phosphorylation of enteroviral 2AJournal of medical virology · 2023
    Article
  5. Article
  6. Article
  7. Review
  8. Enterovirus 2AmBio · 2021
    Article
  9. Article
  10. Article
  11. Deeping in the Role of the MAP-Kinases Interacting Kinases (MNKs) in Cancer.International journal of molecular sciences · 2020
    Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. eIF4E Phosphorylation in Prostate Cancer.Neoplasia (New York, N.Y.) · 2018
    Review
  17. Article
  18. Recombinant Poliovirus for Cancer Immunotherapy.Annual review of medicine · 2018
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Michael C BrownDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA Department of Surgery, Division of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.
Mikhail I DobrikovDepartment of Surgery, Division of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.
Matthias GromeierDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA Department of Surgery, Division of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA grome001@mc.duke.edu.
Duke Medical Center · USDuke University · US

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI DONNA NIEDZWIECKI · 1985 to 2026
$174.8M
Duke CTSA (Composite)UL1TR001117 · NCATS · DUKE UNIVERSITY · PI BOULWARE, LEIGH E, LI, JENNIFER S · 2013 to 2017
$41.3M
Viral Oncology Training GrantT32CA009111 · NCI · DUKE UNIVERSITY · PI LUFTIG, MICAH A. · 1985 to 2023
$8.9M
Targeting Translation Control in Malignant GliomaR01CA124756 · NCI · DUKE UNIVERSITY · PI GROMEIER, MATTHIAS · 2007 to 2016
$2.6M
NCATS NIH HHS UL1 TR001117NCATS NIH HHS UL1TR001117NCI NIH HHS 5T32CA009111NCI NIH HHS CA124756NCI NIH HHS P30 CA014236NCI NIH HHS R01 CA124756NCI NIH HHS T32 CA009111
6 · The paper itself

Abstract

unlabelledTranslation machinery is a major recipient of the principal mitogenic signaling networks involving Raf-ERK1/2 and phosphoinositol 3-kinase (PI3K)-mechanistic target of rapamycin (mTOR). Picornavirus internal ribosomal entry site (IRES)-mediated translation and cytopathogenic effects are susceptible to the status of such signaling cascades in host cells. We determined that tumor-specific cytotoxicity of the poliovirus/rhinovirus chimera PVSRIPO is facilitated by Raf-ERK1/2 signals to the mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) and its effects on the partitioning/activity of the Ser/Arg (SR)-rich protein kinase (SRPK) (M. C. Brown, J. D. Bryant, E. Y. Dobrikova, M. Shveygert, S. S. Bradrick, V. Chandramohan, D. D. Bigner, and M, Gromeier, J. Virol. 22:13135-13148, 2014, doi:http://dx.doi.org/10.1128/JVI.01883-14). Here, we show that MNK regulates SRPK via mTOR and AKT. Our investigations revealed a MNK-controlled mechanism acting on mTORC2-AKT. The resulting suppression of AKT signaling attenuates SRPK activity to enhance picornavirus type 1 IRES translation and favor PVSRIPO tumor cell toxicity and killing. IMPORTANCE: Oncolytic immunotherapy with PVSRIPO, the type 1 live-attenuated poliovirus (PV) (Sabin) vaccine containing a human rhinovirus type 2 (HRV2) IRES, is demonstrating early promise in clinical trials with intratumoral infusion in recurrent glioblastoma (GBM). Our investigations demonstrate that the core mechanistic principle of PVSRIPO, tumor-selective translation and cytotoxicity, relies on constitutive ERK1/2-MNK signals that counteract the deleterious effects of runaway AKT-SRPK activity in malignancy.

Indexed as

Protein BiosynthesisSignal TransductionAnimalsCell LineHumansIntracellular Signaling Peptides and ProteinsMechanistic Target of Rapamycin Complex 2Multiprotein ComplexesOncogene Protein v-aktOncolytic VirusesPoliovirusProtein Serine-Threonine KinasesRhinovirusTOR Serine-Threonine KinasesIntracellular Signaling Peptides and ProteinsMechanistic Target of Rapamycin Complex 2MKNK1 protein, humanMultiprotein ComplexesOncogene Protein v-aktProtein Serine-Threonine KinasesSRPK1 protein, humanTOR Serine-Threonine Kinases

Identifiers

PMID25187540
PMCPMC4249080
OpenAlexW2002336642

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.