Nucleophosmin/B26 regulates PTEN through interaction with HAUSP in acute myeloid leukemia

N. I. Noguera, M. S. Song, M. Divona, G. Catalano, K. L. Calvo, F. García, T. Ottone, F. Florenzano, I. Faraoni, L. Battistini, E. Colombo, S. Amadori, P. P. Pandolfi, F. Lo-Coco

Research output: Contribution to journalArticle

Abstract

PTEN (phosphatase and tensin homolog deleted in chromosome 10) is a bona fide dual lipid and protein phosphatase with cytoplasmic (Cy) and nuclear localization. PTEN nuclear exclusion has been associated with tumorigenesis. Nucleophosmin (NPM1) is frequently mutated in acute myeloid leukemia (AML) and displays Cy localization in mutated nucleophosmin (NPMc+) AML. Here we show that NPM1 directly interacts with herpes virus-associated ubiquitin specific protease (HAUSP), which is known as a PTEN deubiquitinating enzyme. Strikingly, PTEN is aberrantly localized in AML carrying NPMc+. Mechanistically, NPM1 in the nucleus opposes HAUSP-mediated deubiquitination and this promotes the shuttle of PTEN to the cytoplasm. In the cytoplasm, NPMc+ prevents HAUSP from deubiquitinating PTEN, causing the latter to stay in the cytoplasm where it is polyubiquitinated and degraded. Our findings delineate a new NPM1-HAUSP molecular interaction controlling PTEN deubiquitination and trafficking.

Original languageEnglish
Pages (from-to)1037-1043
Number of pages7
JournalLeukemia
Volume27
Issue number5
DOIs
Publication statusPublished - May 2013

Keywords

  • acute myeloid leukemia
  • Hausp
  • PTEN
  • suppressor gene

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

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    Noguera, N. I., Song, M. S., Divona, M., Catalano, G., Calvo, K. L., García, F., Ottone, T., Florenzano, F., Faraoni, I., Battistini, L., Colombo, E., Amadori, S., Pandolfi, P. P., & Lo-Coco, F. (2013). Nucleophosmin/B26 regulates PTEN through interaction with HAUSP in acute myeloid leukemia. Leukemia, 27(5), 1037-1043. https://doi.org/10.1038/leu.2012.314