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

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Gil, Anabel and Rodríguez Escudero, Isabel and Stumpf, Miriam and Molina Martín, María and Jiménez Cid, Víctor and Pulido, Rafael (2015) A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity. PloS one, 10 (4). e0119287. ISSN 1932-6203

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Official URL: http://dx.doi.org/10.1371/ journal.pone.0119287



Abstract

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.


Item Type:Article
Uncontrolled Keywords:PTEN
Subjects:Medical sciences > Pharmacy > Microbiology
ID Code:36190
Deposited On:11 Apr 2016 12:18
Last Modified:20 Apr 2016 11:26

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