2026-06-30T02:00:48Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/83602024-11-29T19:47:48Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc 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 author 2018-04-01 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. 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 2i ERF RAS mESCs Pluripotency ERF deletion rescues RAS deficiency in mouse embryonic stem cells