Gil, AnabelRodríguez Escudero, María IsabelStumpf, MiriamMolina Martín, MaríaJiménez Cid, VíctorPulido, Rafael2023-06-182023-06-182015-04-15Gil, A., Rodríguez Escudero, M. I., Stumpf, M. et al. «A Functional Dissection of PTEN N-Terminus: Implications in PTEN Subcellular Targeting and Tumor Suppressor Activity». PLOS ONE, editado por Vladimir N. Uversky, vol. 10, n.o 4, abril de 2015, p. e0119287. DOI.org (Crossref), https://doi.org/10.1371/journal.pone.0119287.1932-620310.1371/ journal.pone.0119287https://hdl.handle.net/20.500.14352/24375Spatial 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.engAtribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/journal articlehttp://dx.doi.org/10.1371/ journal.pone.0119287open access579PTENMicrobiología (Farmacia)3302.03 Microbiología Industrial