Amb motiu del tancament d'estiu, la validació de documents es reprendrà a partir del 28 d'agost de 2026. Disculpeu les molèsties.
Con motivo del cierre de verano, la validación de documentos se reanudará a partir del 28 de agosto de 2026. Disculpad las molestias
Due to the summer closure, document validation will resume starting August 28, 2026. We apologize for any inconvenience.

Files

s41467-021-26258-z.pdf (1.23 MB)

Document type

Article

Publication date

2021-10-18

Publication license

cc by (c) Diesch, Jeannine et al, 2021
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/181016

Inhibition of CBP synergizes with the RNA-dependent mechanisms of Azacitidine by limiting protein synthesis

Journal Title

Authors

Director/Tutor

Journal ISSN

Volume Title

Related resource

https://doi.org/10.1038/s41467-021-26258-z

Abstract

The nucleotide analogue azacitidine (AZA) is currently the best treatment option for patients with high-risk myelodysplastic syndromes (MDS). However, only half of treated patients respond and of these almost all eventually relapse. New treatment options are urgently needed to improve the clinical management of these patients. Here, we perform a loss-of-function shRNA screen and identify the histone acetyl transferase and transcriptional co-activator, CREB binding protein (CBP), as a major regulator of AZA sensitivity. Compounds inhibiting the activity of CBP and the closely related p300 synergistically reduce viability of MDS-derived AML cell lines when combined with AZA. Importantly, this effect is specific for the RNA-dependent functions of AZA and not observed with the related compound decitabine that is only incorporated into DNA. The identification of immediate target genes leads us to the unexpected finding that the effect of CBP/p300 inhibition is mediated by globally down regulating protein synthesis. © 2021. The Author(s).

Subject

Hematopoesi, Terapèutica

Subject (English)

Hematopoiesis, Therapeutics

Citation

Collections

Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citation

DIESCH, Jeannine, et al. Inhibition of CBP synergizes with the RNA-dependent mechanisms of Azacitidine by limiting protein synthesis. Nature Communications. 2021. Vol. 12, num. 1. ISSN 2041-1723. [consulted: 11 of August of 2026]. Available at: https://hdl.handle.net/2445/181016

Export metadata

JSON - METS

Share record