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oai:docta.ucm.es:20.500.14352/243752024-07-31T15:57:37Zcom_20.500.14352_14col_20.500.14352_15

Gil, Anabel Rodríguez Escudero, María Isabel Stumpf, Miriam Molina Martín, María Jiménez Cid, Víctor Pulido, Rafael 2023-06-18T06:50:37Z 2023-06-18T06:50:37Z 2015-04-15 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. 1932-6203 10.1371/ journal.pone.0119287 https://hdl.handle.net/20.500.14352/24375 http://dx.doi.org/10.1371/ journal.pone.0119287 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. eng https://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity. journal article