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A short N-terminal sequence of PTEN controls cytoplasmic localization and is required for suppression of cell growth

Oncogene volume 26, pages 3930–3940 (2007)Cite this article

Abstract

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an important negative regulator of cell growth and a tumor suppressor. Its growth-attenuating activity is based on the dephosphorylation of phosphatidylinositol 3,4,5-trisphosphate (PIP3), an essential second messenger for the phosphoinositide 3-kinase/Akt signaling pathway. This activity may require localization of PTEN to cytoplasmic membranes. Yet PTEN can also localize to the cell nucleus where its functions remain unclear. Here we present data that define a short sequence in the N-terminal region of PTEN required for cytoplasmic localization. We will refer to this sequence as cytoplasmic localization signal (CLS). It could function as a non-canonical signal for nuclear export or as a cytoplasmic retention signal of PTEN. Mutations within the CLS induce nuclear localization and impair growth suppressive activities of PTEN while preserving lipid phosphatase activity. We propose that nuclear localization of PTEN is not compatible with plasma membrane-targeted growth suppressive functions of PTEN.

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Acknowledgements

The work of the authors is supported by grants from the National Cancer Institute (CA078230, CA078045 and CA94233) and a Fellowship of the American Cancer Society (PF-04-092-01-MGO). This is manuscript number 17452-MEM of The Scripps Research Institute.

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Author notes

  1. G Denning

    Present address: Division of Pediatric Hematology and Oncology, Department of Pediatrics, AFLAC Cancer Center and Blood Disorder Service, Emory School of Medicine, Atlanta, GA, USA

  2. D L Durden and P K Vogt: These authors have contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA

    G Denning & P K Vogt

  2. Division of Pediatric Hematology and Oncology, Department of Pediatrics, AFLAC Cancer Center and Blood Disorder Service, Emory School of Medicine, Atlanta, GA, USA

    B Jean-Joseph, C Prince & D L Durden

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  1. G Denning
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  2. B Jean-Joseph
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Correspondence to G Denning.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Denning, G., Jean-Joseph, B., Prince, C. et al. A short N-terminal sequence of PTEN controls cytoplasmic localization and is required for suppression of cell growth. Oncogene 26, 3930–3940 (2007). https://doi.org/10.1038/sj.onc.1210175

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