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Nuclear Localization of PTEN by a Ran-dependent Mechanism Enhances Apoptosis: Involvement of an N-Terminal Nuclear Localization Domain and Multiple Nuclear Exclusion Motifs

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Nuclear Localization of PTEN by a Ran-dependent Mechanism Enhances Apoptosis: Involvement of an N-Terminal Nuclear Localization Domain and Multiple Nuclear Exclusion Motifs

dc.contributor.author	Gil, Anabel
dc.contributor.author	Andrés-Pons, Amparo
dc.contributor.author	Fernández, Elena
dc.contributor.author	Valiente, Miguel
dc.contributor.author	Torres Ibáñez, José Manuel
dc.contributor.author	Cervera, Javier
dc.contributor.author	Pulido Murillo, Rafael
dc.date.accessioned	2022-11-02T19:06:42Z
dc.date.available	2022-11-02T19:06:42Z
dc.date.issued	2006
dc.identifier.citation	Gil, Anabel Andrés-Pons, Amparo Fernández, Elena Valiente, Miguel Torres Ibáñez, José Manuel Cervera, Javier Pulido Murillo, Rafael 2006 Nuclear Localization of PTEN by a Ran-dependent Mechanism Enhances Apoptosis: Involvement of an N-Terminal Nuclear Localization Domain and Multiple Nuclear Exclusion Motifs Molecular Biology of the Cell 17 9 4002 4013
dc.identifier.uri	https://hdl.handle.net/10550/84375
dc.description.abstract	The targeting of the tumor suppressor PTEN protein to distinct subcellular compartments is a major regulatory mechanism of PTEN function, by controlling its access to substrates and effector proteins. Here, we investigated the molecular basis and functional consequences of PTEN nuclear/cytoplasmic distribution. PTEN accumulated in the nucleus of cells treated with apoptotic stimuli. Nuclear accumulation of PTEN was enhanced by mutations targeting motifs in distinct PTEN domains, and it was dependent on an N-terminal nuclear localization domain. Coexpression of a dominant negative Ran GTPase protein blocked PTEN accumulation in the nucleus, which was also affected by coexpression of importin α proteins. The lipid- and protein-phosphatase activity of PTEN differentially modulated PTEN nuclear accumulation. Furthermore, catalytically active nuclear PTEN enhanced cell apoptotic responses. Our findings indicate that multiple nuclear exclusion motifs and a nuclear localization domain control PTEN nuclear localization by a Ran-dependent mechanism and suggest a proapoptotic role for PTEN in the cell nucleus.
dc.language.iso	eng
dc.relation.ispartof	Molecular Biology of the Cell, 2006, vol. 17, num. 9, p. 4002-4013
dc.subject	Cèl·lules
dc.subject	Proteïnes supressores de tumors
dc.title	Nuclear Localization of PTEN by a Ran-dependent Mechanism Enhances Apoptosis: Involvement of an N-Terminal Nuclear Localization Domain and Multiple Nuclear Exclusion Motifs
dc.type	journal article	es_ES
dc.date.updated	2022-11-02T19:06:42Z
dc.identifier.doi	10.1091/mbc.e06-05-0380
dc.identifier.idgrec	080770
dc.rights.accessRights	open access	es_ES