A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity.

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 si...

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Detalles Bibliográficos
Autores: Gil, Anabel, Rodríguez Escudero, María Isabel, Stumpf, Miriam, Molina Martín, María, Jiménez Cid, Víctor, Pulido, Rafael
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/24375
Acceso en línea:https://hdl.handle.net/20.500.14352/24375
Access Level:acceso abierto
Palabra clave:579
PTEN
Microbiología (Farmacia)
3302.03 Microbiología Industrial
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oai_identifier_str oai:docta.ucm.es:20.500.14352/24375
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network_name_str España
repository_id_str
spelling A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity.Gil, AnabelRodríguez Escudero, María IsabelStumpf, MiriamMolina Martín, MaríaJiménez Cid, VíctorPulido, Rafael579PTENMicrobiología (Farmacia)3302.03 Microbiología IndustrialSpatial 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.Universidad Complutense de Madrid20152015-04-1520152015-04-15journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/24375reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/243752026-06-02T12:44:21Z
dc.title.none.fl_str_mv A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity.
title A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity.
spellingShingle A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity.
Gil, Anabel
579
PTEN
Microbiología (Farmacia)
3302.03 Microbiología Industrial
title_short A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity.
title_full A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity.
title_fullStr A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity.
title_full_unstemmed A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity.
title_sort A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity.
dc.creator.none.fl_str_mv Gil, Anabel
Rodríguez Escudero, María Isabel
Stumpf, Miriam
Molina Martín, María
Jiménez Cid, Víctor
Pulido, Rafael
author Gil, Anabel
author_facet Gil, Anabel
Rodríguez Escudero, María Isabel
Stumpf, Miriam
Molina Martín, María
Jiménez Cid, Víctor
Pulido, Rafael
author_role author
author2 Rodríguez Escudero, María Isabel
Stumpf, Miriam
Molina Martín, María
Jiménez Cid, Víctor
Pulido, Rafael
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 579
PTEN
Microbiología (Farmacia)
3302.03 Microbiología Industrial
topic 579
PTEN
Microbiología (Farmacia)
3302.03 Microbiología Industrial
description 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.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-04-15
2015
2015-04-15
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/24375
url https://hdl.handle.net/20.500.14352/24375
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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