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SUMO conjugation susceptibility of Akt/protein kinase B affects the expression of the pluripotency transcription factor Nanog in embryonic stem cells

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dc.contributor.author Francia, Marcos
dc.contributor.author Stortz, Martin
dc.contributor.author Vazquez Echegaray, Camila
dc.contributor.author Oses, Camila
dc.contributor.author Verneri, Paula
dc.contributor.author Petrone, María Victoria
dc.contributor.author Toro, Ayelén
dc.contributor.author Waisman, Ariel
dc.contributor.author Miriuka, Santiago Gabriel
dc.contributor.author Cosentino, María Soledad
dc.contributor.author Levi, Valeria
dc.contributor.author Guberman, Alejandra S.
dc.date.accessioned 2021-08-31T13:48:02Z
dc.date.available 2021-08-31T13:48:02Z
dc.date.issued 2021-07-09
dc.identifier.citation Francia M, Stortz M, Echegaray CV, Oses C, Verneri P, Petrone MV, Toro A, Waisman A, Miriuka S, Cosentino MS, Levi V, Guberman AS. SUMO conjugation susceptibility of Akt/protein kinase B affects the expression of the pluripotency transcription factor Nanog in embryonic stem cells. PLoS One. 2021 Jul 9;16(7):e0254447. doi: 10.1371/journal.pone.0254447 es_ES
dc.identifier.uri https://doi.org/10.1371/journal.pone.0254447
dc.identifier.uri https://repositorio.fleni.org.ar/xmlui/handle/123456789/563
dc.description.abstract Akt/PKB is a kinase involved in the regulation of a wide variety of cell processes. Its activity is modulated by diverse post-translational modifications (PTMs). Particularly, conjugation of the small ubiquitin-related modifier (SUMO) to this kinase impacts on multiple cellular functions, such as proliferation and splicing. In embryonic stem (ES) cells, this kinase is key for pluripotency maintenance. Among other functions, Akt is known to promote the expression of Nanog, a central pluripotency transcription factor (TF). However, the relevance of this specific PTM of Akt has not been previously analyzed in this context. In this work, we study the effect of Akt1 variants with differential SUMOylation susceptibility on the expression of Nanog. Our results demonstrate that both, the Akt1 capability of being modified by SUMO conjugation and a functional SUMO conjugase activity are required to induce Nanog gene expression. Likewise, we found that the common oncogenic E17K Akt1 mutant affected Nanog expression in ES cells also in a SUMOylatability dependent manner. Interestingly, this outcome takes places in ES cells but not in a non-pluripotent heterologous system, suggesting the presence of a crucial factor for this induction in ES cells. Remarkably, the two major candidate factors to mediate this induction, GSK3-β and Tbx3, are non-essential players of this effect, suggesting a complex mechanism probably involving non-canonical pathways. Furthermore, we found that Akt1 subcellular distribution does not depend on its SUMOylatability, indicating that Akt localization has no influence on the effect on Nanog, and that besides the membrane localization of E17K Akt mutant, SUMOylation is also required for its hyperactivity. Our results highlight the impact of SUMO conjugation in the function of a kinase relevant for a plethora of cellular processes, including the control of a key pluripotency TF. es_ES
dc.language.iso eng es_ES
dc.publisher Public Library of Science es_ES
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/2.5/ar/
dc.subject Small Ubiquitin-Related Modifier Proteins es_ES
dc.subject Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina es_ES
dc.subject Sumoylation es_ES
dc.subject Sumoilación es_ES
dc.subject AKT1 protein es_ES
dc.subject Proteína AKT1 es_ES
dc.subject NANOG protein es_ES
dc.subject Proteína Nanog es_ES
dc.subject Embryonic Stem Cells es_ES
dc.subject Células Madre Embrionarias es_ES
dc.title SUMO conjugation susceptibility of Akt/protein kinase B affects the expression of the pluripotency transcription factor Nanog in embryonic stem cells es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.type info:eu-repo/semantics/publishedVersion
dc.description.fil Fil: Francia, Marcos. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica. Departamento de Química Biológica; Argentina.
dc.description.fil Fil: Stortz, Martin. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica. Departamento de Química Biológica; Argentina.
dc.description.fil Fil: Vazquez Echegaray, Camila. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica. Departamento de Química Biológica; Argentina.
dc.description.fil Fil: Oses, Camila. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica. Departamento de Química Biológica; Argentina.
dc.description.fil Fil: Verneri, Paula. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica. Departamento de Química Biológica; Argentina.
dc.description.fil Fil: Petrone, María Victoria. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica. Departamento de Química Biológica; Argentina.
dc.description.fil Fil: Toro, Ayelén. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica. Departamento de Química Biológica; Argentina.
dc.description.fil Fil: Waisman, Ariel. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.
dc.description.fil Fil: Miriuka, Santiago. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.
dc.description.fil Fil: Cosentino, María Soledad. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica. Departamento de Química Biológica; Argentina.
dc.description.fil Fil: Levi, Valeria. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica. Departamento de Química Biológica; Argentina.
dc.description.fil Fil: Guberman, Alejandra S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica. Departamento de Química Biológica; Argentina.
dc.relation.ispartofVOLUME 16
dc.relation.ispartofNUMBER 7
dc.relation.ispartofPAGINATION e0254447
dc.relation.ispartofCOUNTRY Estados Unidos
dc.relation.ispartofCITY San Francisco
dc.relation.ispartofTITLE PloS one
dc.relation.ispartofISSN 1932-6203
dc.type.snrd info:ar-repo/semantics/artículo es_ES


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