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PTEN enters the nucleus by diffusion

Authors

  • Fenghua Liu,

    1. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605
    Current affiliation:
    1. Harvard Medical School, Boston, Massachusetts 02115.
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  • Stefan Wagner,

    1. Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655
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  • Robert B. Campbell,

    1. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605
    Current affiliation:
    1. Charles River Discovery and Development Services, Worcester, Massachusetts 01608, USA.
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  • Jeffrey A. Nickerson,

    1. Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655
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  • Celia A. Schiffer,

    1. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605
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  • Alonzo H. Ross

    Corresponding author
    1. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605
    • Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605.
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Errata

This article is corrected by:

  1. Errata: PTEN Enters the Nucleus by Diffusion. Fenghua Liu, Stefan Wagner, Robert B. Campbell, Jeffrey A. Nickerson, Celia A. Schiffer, and Alonzo H. Ross Volume 117, Issue 3, 806, Article first published online: 20 January 2016

Abstract

Despite much evidence for phosphatidylinositol phosphate (PIP)-triggered signaling pathways in the nucleus, there is little understanding of how the levels and activities of these proteins are regulated. As a first step to elucidating this problem, we determined whether phosphatase and tensin homolog deleted on chromosome 10 (PTEN) enters the nucleus by passive diffusion or active transport. We expressed various PTEN fusion proteins in tsBN2, HeLa, LNCaP, and U87MG cells and determined that the largest PTEN fusion proteins showed little or no nuclear localization. Because diffusion through nuclear pores is limited to proteins of 60,000 Da or less, this suggests that nuclear translocation of PTEN occurs via diffusion. We examined PTEN mutants, seeking to identify a nuclear localization signal (NLS) for PTEN. Mutation of K13 and R14 decreased nuclear localization, but these amino acids do not appear to be part of an NLS. We used fluorescence recovery after photobleaching (FRAP) to demonstrate that GFP-PTEN can passively pass through nuclear pores. Diffusion in the cytoplasm is retarded for the PTEN mutants that show reduced nuclear localization. We conclude that PTEN enters the nucleus by diffusion. In addition, sequestration of PTEN in the cytoplasm likely limits PTEN nuclear translocation. © 2005 Wiley-Liss, Inc.

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