PTEN levels are controlled by a nuclear transport receptor in lung cancer

Chen, M. H., Herzka, T. M., Zeeman, M. E., Plafker, K. S., Minderer, M., Castillo-Martin, M., Cordon-Cardo, C., Plafker, S. M., Trotman, L. C. (April 2013) PTEN levels are controlled by a nuclear transport receptor in lung cancer. Cancer Research, 73 (8 (Sup). p. 5258. ISSN 0008-5472

URL: http://cancerres.aacrjournals.org/cgi/content/shor...
DOI: 10.1158/1538-7445.am2013-5258

Abstract

The maintenance of PTEN protein levels is critical for tumor suppression. Yet, the ubiquitination system has been shown to affect PTEN levels both adversely through degradation, as well as positively through nuclear import, and it has remained unclear how these two processes are integrated to prevent cancer. Here we show, that a nuclear import receptor is at the heart of a failsafe system that maintains PTEN levels by mediating its nuclear transport. Loss of import receptor function not only leads to cytoplasmic PTEN accumulation but also prompts PTEN degradation through a novel component of the PTEN ubiquitination system. By testing the consequences of importin loss in vivo, we found that hypomorphic mice developed lung adenocarcinoma, which presented with aberrant cytoplasmic PTEN localization and degradation, as predicted by our in vitro findings. Since the corresponding human locus suffers frequent deletion as well as inactivating mutations in lung cancer, we propose that this import receptor is a novel tumor suppressor that antagonizes PI 3-Kinase signaling in settings with at least one intact PTEN gene.

Item Type: Paper
Additional Information: Meeting Abstract
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > PTEN
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
diseases & disorders > cancer > cancer types > lung cancer
Publication Type > Meeting Abstract
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > tumor suppressor
CSHL Authors:
Communities: CSHL labs > Trotman lab
Depositing User: Matt Covey
Date: April 2013
Date Deposited: 11 Apr 2014 16:41
Last Modified: 12 Feb 2018 17:32
URI: http://repository.cshl.edu/id/eprint/29753

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