Evidence map›Paper›PMID 39554175›Full record

ArticlebioRxiv : the preprint server for biology2024

Endogenous EWSR1-FLI1 degron alleles enable control of fusion oncoprotein expression in tumor cell lines and xenografts.

James H McGinnis, Alberto Bremauntz Enriquez, Florentina Vandiver, Xin Bai, Jiwoong Kim, Jessica Kilgore, Purbita Saha, Ryan O'Hara, Yang Xie, Laura A Banaszynski and 2 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

James H McGinnisDepartment of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.
Alberto Bremauntz EnriquezDepartment of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.ORCID 0000-0002-1216-3099
Florentina VandiverDepartment of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.
Xin BaiDepartment of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.
Jiwoong KimQuantitative Biomedical Research Center, Peter O'Donnell School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.
Jessica KilgoreDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.
Purbita SahaCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.
Ryan O'HaraCecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.
Yang XieQuantitative Biomedical Research Center, Peter O'Donnell School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.
Laura A BanaszynskiHarold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.ORCID 0000-0002-5189-8848
Noelle WilliamsDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.ORCID 0000-0003-1894-5742
David G McFaddenDepartment of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.ORCID 0000-0001-8466-2199

Funding

Targeting EWSR1-FLI1 through Functional, Structural and Chemical ApproachesU54CA231649 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI MCKNIGHT, STEVEN L · 2019 to 2019
$10.0M
Chromatin Dynamics and Genome RegulationR35GM124958 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI Laura Banaszynski · 2017 to 2026
$4.4M
Mechanisms of p300 Activation During Pluripotency and Differentiation.R01HD109239 · NICHD · UT SOUTHWESTERN MEDICAL CENTER · PI Laura Banaszynski · 2022 to 2026
$2.1M
NCI NIH HHS U54 CA231649NICHD NIH HHS R01 HD109239NIGMS NIH HHS R35 GM124958
6 · The paper itself

Abstract

Pediatric malignancies frequently harbor chromosomal translocations that induce expression of fusion oncoproteins. The EWSR1-FLI1 fusion oncoprotein acts as a neomorphic transcription factor and is the dominant genetic driver of Ewing's sarcoma. Interrogation of the mechanisms by which EWSR1-FLI1 drives tumorigenesis has been limited by a lack of model systems to precisely and selectively control its expression in patient-derived cell lines and xenografts. Here, we report the generation of a panel of patient-derived EWS cell lines in which inducible protein degrons were engineered into the endogenous EWSR1-FLI1 locus. These alleles enabled rapid and efficient depletion of EWSR1-FLI1. Complete suppression of EWSR1-FLI1 induced a reversible cell cycle arrest at the G

Indexed as

auxin-inducible degronEwing’s sarcomaEWSR1-FLI1fusion oncoproteininducible degronsmall molecule assisted shutoffxenograft

Identifiers

PMID39554175
PMCPMC11566046

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.