RT Journal Article
T1 Expression of Human PTEN-L in a Yeast Heterologous Model Unveils Specific N-Terminal Motifs Controlling PTEN-L Subcellular Localization and Function
A1 Fernández-Acero Bascones, Teresa
A1 Bertalmio, Eleonora
A1 Luna, Sandra
A1 Mingo, Janire
A1 Bravo Plaza, Ignacio
A1 Rodríguez Escudero, María Isabel
A1 Molina Martín, María
A1 Pulido, Rafael
A1 Jiménez Cid, Víctor
AB 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.
PB MDPI
SN 2073-4409
YR 2019
FD 2019-11-26
LK https://hdl.handle.net/20.500.14352/8315
UL https://hdl.handle.net/20.500.14352/8315
LA eng
NO Fernández-Acero Bascones, T., Bertalmio, E., Luna, S. et al. «Expression of Human PTEN-L in a Yeast Heterologous Model Unveils Specific N-Terminal Motifs Controlling PTEN-L Subcellular Localization and Function». Cells, vol. 8, n.o 12, noviembre de 2019, p. 1512. DOI.org (Crossref), https://doi.org/10.3390/cells8121512.
NO Ministerio de Economía, Comercio y Empresa (España)
NO Comunidad de Madrid/Fondo Europeo de Desarrollo Regional
DS Docta Complutense
RD 25 dic 2025