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Updated: May 16, 2026

Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH
Published on: August 19, 2014
Nucleophosmin/B26 regulates PTEN through interaction with HAUSP in acute myeloid leukemia
N I Noguera1, M S Song, M Divona
1Neuro-Oncoematology Unit, Santa Lucia Foundation, Rome, Italy. n.noguera@hsantalucia.it
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.
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