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Título:
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A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity.
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Autores:
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Gil, Anabel ;
Rodríguez Escudero, Isabel ;
Stumpf, Miriam ;
Molina Martín, María ;
Jiménez Cid, Víctor ;
Pulido, Rafael
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Tipo de documento:
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texto impreso
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Fecha de publicación:
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2015-04-15
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Dimensiones:
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application/pdf
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Nota general:
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cc_by
info:eu-repo/semantics/openAccess
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Idiomas:
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Palabras clave:
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Estado = Publicado
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Materia = Ciencias Biomédicas: Farmacia: Microbiología
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Tipo = Artículo
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Resumen:
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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.
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En línea:
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https://eprints.ucm.es/36190/1/Gil.PLOS2015.pdf
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