Evidence map›Paper›PMID 25564528›Full record

ArticleNucleic acids research2015

RNA helicase A activity is inhibited by oncogenic transcription factor EWS-FLI1.

Hayriye Verda Erkizan, Jeffrey A Schneider, Kamal Sajwan, Garrett T Graham, Brittany Griffin, Sergey Chasovskikh, Sarah E Youbi, Abraham Kallarakal, Maksymilian Chruszcz, Radhakrishnan Padmanabhan and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

26 citing papers in PubMed, 41 citations in OpenAlex.

  1. Open-Label, Multicenter, Phase I/II, First-in-Human Trial of TK216: A First-Generation EWS::FLI1 Fusion Protein Antagonist in Ewing Sarcoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024
    Trial
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  11. Cancers · 2022
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  14. RNA-binding proteins of COSMIC importance in cancer.The Journal of clinical investigation · 2021
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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

13 authors at 3 institutions in 1 country.

Hayriye Verda ErkizanDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road NW, New Research Building E316, Washington, DC 20007, USA hve2@georgetown.edu.
Jeffrey A SchneiderDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road NW, New Research Building E316, Washington, DC 20007, USA.
Kamal SajwanDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road NW, New Research Building E316, Washington, DC 20007, USA.
Garrett T GrahamDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road NW, New Research Building E316, Washington, DC 20007, USA.
Brittany GriffinDepartment of Microbiology and Immunology, Georgetown University Medical Center, SW 309 Med-Dent, Washington, DC 20007, USA.
Sergey ChasovskikhDepartment of Radiation Medicine, Georgetown University Medical Center, 3970 Reservoir Road NW, New Research Building E220, Washington, DC 20007, USA.
Sarah E YoubiDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road NW, New Research Building E316, Washington, DC 20007, USA.
Abraham KallarakalDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road NW, New Research Building E316, Washington, DC 20007, USA.
Maksymilian ChruszczDepartment of Chemistry and Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, SC 29208, USA.
Radhakrishnan PadmanabhanDepartment of Microbiology and Immunology, Georgetown University Medical Center, SW 309 Med-Dent, Washington, DC 20007, USA.
John L CaseyDepartment of Microbiology and Immunology, Georgetown University Medical Center, SW 309 Med-Dent, Washington, DC 20007, USA.
Aykut ÜrenDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road NW, New Research Building E316, Washington, DC 20007, USA.
Jeffrey A ToretskyDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road NW, New Research Building E316, Washington, DC 20007, USA.
Georgetown University · USGeorgetown University Medical Center · USUniversity of South Carolina Sumter · US

Funding

Tissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI STEPHEN W BYERS · 1990 to 2026
$71.5M
YK-4-279 specifically targets ETS family fusion-protein cancers in clinical trialRC4CA156509 · NCI · GEORGETOWN UNIVERSITY · PI TORETSKY, JEFFREY A · 2010 to 2010
$4.4M
Isolation and small molecule targeting of Ewing's Sarcoma stem cellsR01CA138212 · NCI · GEORGETOWN UNIVERSITY · PI TORETSKY, JEFFREY A · 2008 to 2012
$2.4M
Novel Compounds to Inactivate Oncogenic Fusion ProteinsR01CA133662 · NCI · GEORGETOWN UNIVERSITY · PI TORETSKY, JEFFREY A · 2009 to 2013
$1.5M
NCI NIH HHS P30 CA051008NCI NIH HHS P30 CA051008-16NCI NIH HHS R01 CA133662NCI NIH HHS R01CA133662NCI NIH HHS R01 CA138212NCI NIH HHS R01CA138212NCI NIH HHS RC4 CA156509NCI NIH HHS RC4CA156509
6 · The paper itself

Abstract

RNA helicases impact RNA structure and metabolism from transcription through translation, in part through protein interactions with transcription factors. However, there is limited knowledge on the role of transcription factor influence upon helicase activity. RNA helicase A (RHA) is a DExH-box RNA helicase that plays multiple roles in cellular biology, some functions requiring its activity as a helicase while others as a protein scaffold. The oncogenic transcription factor EWS-FLI1 requires RHA to enable Ewing sarcoma (ES) oncogenesis and growth; a small molecule, YK-4-279 disrupts this complex in cells. Our current study investigates the effect of EWS-FLI1 upon RHA helicase activity. We found that EWS-FLI1 reduces RHA helicase activity in a dose-dependent manner without affecting intrinsic ATPase activity; however, the RHA kinetics indicated a complex model. Using separated enantiomers, only (S)-YK-4-279 reverses the EWS-FLI1 inhibition of RHA helicase activity. We report a novel RNA binding property of EWS-FLI1 leading us to discover that YK-4-279 inhibition of RHA binding to EWS-FLI1 altered the RNA binding profile of both proteins. We conclude that EWS-FLI1 modulates RHA helicase activity causing changes in overall transcriptome processing. These findings could lead to both enhanced understanding of oncogenesis and provide targets for therapy.

Indexed as

DEAD-box RNA HelicasesIndolesModels, MolecularNeoplasm ProteinsOncogene Proteins, FusionProto-Oncogene Protein c-fli-1Recombinant ProteinsRNARNA-Binding Protein EWSDEAD-box RNA HelicasesDHX9 protein, humanEWS-FLI fusion proteinIndolesNeoplasm ProteinsOncogene Proteins, FusionProto-Oncogene Protein c-fli-1Recombinant ProteinsRNARNA-Binding Protein EWSYK 4-279

Identifiers

PMID25564528
PMCPMC4333382
OpenAlexW2161247151

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.