Person:
Rodríguez Escudero, María Isabel

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First Name
María Isabel
Last Name
Rodríguez Escudero
URI
https://hdl.handle.net/20.500.14352/77769
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Microbiología y Parasitología
Area
Microbiología
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2015 - 20194
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Author: Molina Martín, María × End date: 2019 ×

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Now showing 1 - 4 of 4
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    Heterologous mammalian Akt disrupts plasma membrane homeostasis by taking over TORC2 signaling in Saccharomyces cerevisiae
    (Scientific Reports, 2018) Rodríguez Escudero, María Isabel; Fernández-Acero Bascones, Teresa; Jiménez Cid, Víctor; Molina Martín, María
    The Akt protein kinase is the main transducer of phosphatidylinositol-3,4,5-trisphosphate (PtdIns3,4,5P3) signaling in higher eukaryotes, controlling cell growth, motility, proliferation and survival. By co-expression of mammalian class I phosphatidylinositol 3-kinase (PI3K) and Akt in the Saccharomyces cerevisiae heterologous model, we previously described an inhibitory effect on yeast growth that relied on Akt kinase activity. Here we report that PI3K-Akt expression in yeast triggers the formation of large plasma membrane (PM) invaginations that were marked by actin patches, enriched in PtdIns4,5P2 and associated to abnormal intracellular cell wall deposits. These effects of Akt were mimicked by overproduction of the PtdIns4,5P2 effector Slm1, an adaptor of the Ypk1 and Ypk2 kinases in the TORC2 pathway. Although Slm1 was phosphorylated in vivo by Akt, TORC2-dependent Ypk1 activation did not occur. However, PI3K-activated Akt suppressed the lethality derived from inactivation of either TORC2 or Ypk protein kinases. Thus, heterologous co-expression of PI3K and Akt in yeast short-circuits PtdIns4,5P2- and TORC2-signaling at the level of the Slm-Ypk complex, overriding some of its functions. Our results underscore the importance of phosphoinositide-dependent kinases as key actors in the homeostasis and dynamics of the PM.
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    Project number: 265
    SWI@UCM 2.0: Consolidación de Small World Initiative: descubrimiento y uso racional de antibióticos mediante aprendizaje-servicio en la Comunidad de Madrid
    (2018) Jiménez Cid, Víctor; Rodríguez Escudero, María Isabel; Díez Orejas, Rosalía María; Molina Martín, María; Rodríguez Fernández, Carmina; Navarro García, Federico; Arroyo Nombela, Francisco Javier; Román González, Elvira; Martín Brieva, Humberto; Fernández-Acero Bascones, Teresa; Sanz Santamaría, Ana Belén; Díaz Del Toro, Silvia; Calvo De Pablo, Pilar; Patiño Álvarez, Aurora Belén; González Zorn, Bruno; Suárez Rodríguez, Mónica; Goyache Goñi, Joaquín; Escudero García-Calderón, José Antonio; Prieto Prieto, Antonio Daniel; Ugarte Ruiz, María; Gil Serna, Jessica
    Durante el curso anterior un equipo de la UCM en el marco de un proyecto previo INNOVA-Docencia UCM instauró en España de manera pionera la iniciativa de aprendizaje activo Small World Initiative, de origen norteamericano. Los objetivos de esta iniciativa son (1) Crear cultura científica y acercar la investigación biomédica a niveles educativos en los que los estudiantes tienen aún capacidad de decisión sobre su futura orientación formativa con el fin de fomentar la vocación en I+D; y (2) Promover la concienciación social sobre el uso racional de los antibióticos y la amenaza de la resistencia bacteriana a estos fármacos. En el entorno español se propuso implementar esta estrategia mediante Aprendizaje-Servicio. En esta segunda edición (SWI@UCM 2.0) se ha trabajado en la consolidación, expansión y mejora del proyecto, con énfasis en la integración de los diversos niveles educativos que integran el proyecto (universitario y preuniversitario) y la divulgación científica.
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    Expression of Human PTEN-L in a Yeast Heterologous Model Unveils Specific N-Terminal Motifs Controlling PTEN-L Subcellular Localization and Function
    (Cells, 2019) Fernández-Acero Bascones, Teresa; Bertalmio, Eleonora; Luna, Sandra; Mingo, Janire; Bravo Plaza, Ignacio; Rodríguez Escudero, María Isabel; Molina Martín, María; Pulido, Rafael; Jiménez Cid, Víctor
    The tumour suppressor PTEN is frequently downregulated, mutated or lost in several types of tumours and congenital disorders including PHTS (PTEN Hamartoma Tumour Syndrome) and ASD (Autism Spectrum Disorder). PTEN is a lipid phosphatase whose activity over the lipid messenger PIP3 counteracts the stimulation of the oncogenic phosphatidylinositol 3-kinase (PI3K) pathway. Recently, several extended versions of PTEN produced in the cell by alternative translation initiation have been described, among which, PTEN-L and PTEN-M represent the longest isoforms. We previously developed a humanized yeast model in which the expression of PI3K in Saccharomyces cerevisiae led to growth inhibition that could be suppressed by co-expression of PTEN. Here, we show that the expression of PTEN-L and PTEN-M in yeast results in robust counteracting of PI3K-dependent growth inhibition. N-terminally tagged GFP-PTEN-L was sharply localized at the yeast plasma membrane. Point mutations of a putative membrane-binding helix located at the PTEN-L extension or its deletion shifted localization to nuclear. Also, a shift from plasma membrane to nucleus was observed in mutants at basic amino acid clusters at the PIP2-binding motif, and at the Cα2 and CBR3 loops at the C2 domain. In contrast, C-terminally tagged PTEN-L-GFP displayed mitochondrial localization in yeast, which was shifted to plasma membrane by removing the first 22 PTEN-L residues. Our results suggest an important role of the N-terminal extension of alternative PTEN isoforms on their spatial and functional regulation.
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    A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity.
    (PloS one, 2015) Gil, Anabel; Rodríguez Escudero, María Isabel; Stumpf, Miriam; Molina Martín, María; Jiménez Cid, Víctor; Pulido, Rafael
    Spatial regulation of the tumor suppressor PTEN is exerted through alternative plasma membrane, cytoplasmic, and nuclear subcellular locations. The N-terminal region of PTEN is important for the control of PTEN subcellular localization and function. It contains both an active nuclear localization signal (NLS) and an overlapping PIP2-binding motif (PBM) involved in plasma membrane targeting. We report a comprehensive mutational and functional analysis of the PTEN N-terminus, including a panel of tumor-related mutations at this region. Nuclear/cytoplasmic partitioning in mammalian cells and PIP3 phosphatase assays in reconstituted S. cerevisiae defined categories of PTEN N-terminal mutations with distinct PIP3 phosphatase and nuclear accumulation properties. Noticeably, most tumor-related mutations that lost PIP3 phosphatase activity also displayed impaired nuclear localization. Cell proliferation and soft-agar colony formation analysis in mammalian cells of mutations with distinctive nuclear accumulation and catalytic activity patterns suggested a contribution of both properties to PTEN tumor suppressor activity. Our functional dissection of the PTEN N-terminus provides the basis for a systematic analysis of tumor-related and experimentally engineered PTEN mutations.