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A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity. Gil, Anabel Rodríguez Escudero, María Isabel Stumpf, Miriam Molina Martín, María Jiménez Cid, Víctor Pulido, Rafael 579 PTEN Microbiología (Farmacia) 3302.03 Microbiología Industrial 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. Ministerio de Ciencia, Innovación y Universidades (España)/Fondo Europeo de Desarrollo Regional Ministerio de Economía, Comercio y Empresa (España) Comunidad de Madrid Depto. de Microbiología y Parasitología Fac. de Farmacia TRUE pub 2023-06-18T06:50:37Z 2023-06-18T06:50:37Z 2015-04-15 journal article https://hdl.handle.net/20.500.14352/24375 1932-6203 10.1371/ journal.pone.0119287 eng SAF2009-10226 SAF2013-48812-R BIO2010-22369-C02-01 PRIMPOL (S2011/BMD-2414) Gil, 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. Atribución 3.0 España https://creativecommons.org/licenses/by/3.0/es/ open access application/pdf