RT Journal Article
T1 A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity.
A1 Gil, Anabel
A1 Rodríguez Escudero, María Isabel
A1 Stumpf, Miriam
A1 Molina Martín, María
A1 Jiménez Cid, Víctor
A1 Pulido, Rafael
AB 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.
SN 1932-6203
YR 2015
FD 2015-04-15
LK https://hdl.handle.net/20.500.14352/24375
UL https://hdl.handle.net/20.500.14352/24375
LA eng
NO 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.
NO Ministerio de Ciencia, Innovación y Universidades (España)/Fondo Europeo de Desarrollo Regional
NO Ministerio de Economía, Comercio y Empresa (España)
NO Comunidad de Madrid
DS Docta Complutense
RD 7 abr 2025