Related Experiment Video
Updated: Dec 4, 2025

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis
Sara Sánchez-Molina1, Elisabet Figuerola-Bou2, Enrique Blanco3,4
1Developmental Tumor Biology Laboratory, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain. ssanchez@fsjd.org luciano.dicroce@crg.es jmora@sjdhospitalbarcelona.org.
Abstract:
Ewing sarcoma (EwS) is an aggressive tumor that affects adolescents and young adults. EwS is defined by a chromosomal translocation, EWSR1-FLI1 being the most common, that causes genome reprogramming through remodeling of enhancers. Here, we describe an unexpected function of RING1B, which is highly expressed in EwS. While retaining its repressive activity at Polycomb developmental regulated genes, RING1B colocalizes with EWSR1-FLI1 at active enhancers. We demonstrate that RING1B is necessary for the expression of key EWSR1-FLI1 targets by facilitating oncogene recruitment to their enhancers. Knockdown of RING1B impairs growth of tumor xenografts and expression of genes regulated by EWSR1-FLI1 bound enhancers. Pharmacological inhibition of AURKB with AZD1152 increases H2Aub levels causing down-regulation of RING1B/EWSR1-FLI1 common targets. Our findings demonstrate that RING1B is a critical modulator of EWSR1-FLI1-induced chromatin remodeling, and its inhibition is a potential therapeutic strategy for the treatment of these tumors.
More Related Videos
Related Concept Videos
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
Regulation of the Unfolded Protein Response
Restarting Stalled Replication Forks
Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Conservative Site-specific Recombination and Phase Variation
The recognition sites for Cre recombinase called LoxP...
Nucleosome Remodeling
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...

