The SUMO conjugation capability of Akt affects the expression of the pluripotency transcription factor Nanog in mouse embryonic stem cells

GUBERMAN A; MARCOS FRANCIA, CAMILA VÁZQUEZ ECHEGARAY, MARTIN STORTZ, MARÍA VICTORIA PETRONE, AYELEN TORO, VALERIA LEVI AND ALEJANDRA GUBERMAN

CABA

Congreso; Xth meeting of the Latin American Society for Developmental Biology (LASDB) 2019; 2019

Embryonic stemcells (ESCs) are an excellent model to study molecular mechanisms involved inearly development. The transcription factors (TFs) Nanog, Oct4 and Sox2 promotepluripotency and repress differentiation. In cell culture, pluripotency isclassically preserved by serum and LIF. This cytokine turns on multiplesignaling pathways, among them, the PI3K/AKT pathway, which is crucial for self-renewaland pluripotency maintenance. Modification of Akt by SUMO conjugation regulatesits activity in different cell lines and cancer, however, its role in ESCs hasnot been studied yet.In this work we studiedthe effect of the SUMO conjugation of Akt1 on Nanog gene regulation. We usedAkt1 variants with different capability of being SUMOylated. We evaluated theireffect on Nanog gene promoter and on the endogenous Nanog protein. We found thatthose variants that can be SUMOylated induced Nanog gene, however, this effect wascompletely absent with those variants in which SUMO conjugation is diminished. Tostudy the molecular mechanism involved, we analyzed the effect of putative mediators?downregulation by shRNA.  We found that the SUMO conjugation capability ofAkt affects the expression of the pluripotency TF Nanog. Our results suggestthat neither Oct4, Sox2 nor Nanog itself are responsible for the effectproduced by the Akt1 variants on Nanog promoter. We are conducting furtherresearch to unravel the molecular mechanism involved, focusing on a strongcandidate, the TF Tbx3.