Carregant...
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/173808
RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
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.
Matèries
Matèries (anglès)
Citació
Citació
SÁNCHEZ MOLINA, Sara, FIGUEROLA BOU, Elisabet, BLANCO, Enrique, SÁNCHEZ JIMÉNEZ, María, TÁBOAS, Pablo, GÓMEZ, Soledad, BALLARE, Cecilia, GARCÍA DOMÍNGUEZ, Daniel j., PRADA, Estela, HONTECILLAS PRIETO, Lourdes, CARCABOSO, Ángel m., TIRADO, Oscar m., HERNÁNDEZ MUÑOZ, Inmaculada, ÁLAVA, Enrique de, LAVARINO, Cinzia, CROCE, Luciano di, MORA SALVADOR, Jaume. RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis. _Science Advances_. 2020. Vol. 6, núm. 43. [consulta: 20 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/173808]