2026-06-30T02:00:50Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/83602024-11-29T19:47:48Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Mayor-Ruiz, Cristina
author
Olbrich, Teresa
author
Drosten, Matthias
author
Lecona, Emilio
author
Vega-Sendino, Maria
author
Ortega Jimenez, Sagrario
author
Dominguez, Orlando
author
Barbacid, Mariano
author
Ruiz, Sergio
author
Fernandez-Capetillo, Oscar
funder
Fundación La Caixa
funder
Boehringer Ingelheim Fonds
funder
Botín Foundation
funder
Banco Santander
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Ministerio de Economía y Competitividad (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación La Marató TV3
funder
Howard Hughes Medical Institute
2019-09-20T12:10:49Z
2019-09-20T12:10:49Z
2018-04-01
Genes Dev. 2018;32(7-8):568-576
10.1101/gad.310086.117
1549-5477
0890-9369
Genes & development
29650524
http://hdl.handle.net/20.500.12105/8360
MEK inhibition in combination with a glycogen synthase kinase-3β (GSK3β) inhibitor, referred as the 2i condition, favors pluripotency in embryonic stem cells (ESCs). However, the mechanisms by which the 2i condition limits ESC differentiation and whether RAS proteins are involved in this phenomenon remain poorly understood. Here we show that RAS nullyzygosity reduces the growth of mouse ESCs (mESCs) and prohibits their differentiation. Upon RAS deficiency or MEK inhibition, ERF (E twenty-six 2 [Ets2]-repressive factor), a transcriptional repressor from the ETS domain family, translocates to the nucleus, where it binds to the enhancers of pluripotency factors and key RAS targets. Remarkably, deletion of Erf rescues the proliferative defects of RAS-devoid mESCs and restores their capacity to differentiate. Furthermore, we show that Erf loss enables the development of RAS nullyzygous teratomas. In summary, this work reveals an essential role for RAS proteins in pluripotency and identifies ERF as a key mediator of the response to RAS/MEK/ERK inhibition in mESCs.
eng
2i
ERF
RAS
mESCs
Pluripotency
ERF deletion rescues RAS deficiency in mouse embryonic stem cells
journal article
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ERFdeletionrescuesRAS_2018.pdf.txt
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ERFdeletionrescuesRAS_supl_2018.pdf.txt