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

doi:10.1038/leu.2012.314

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 journal › Article › peer-review

44 Scopus citations

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 language	English (US)
Pages (from-to)	1037-1043
Number of pages	7
Journal	Leukemia
Volume	27
Issue number	5
DOIs	https://doi.org/10.1038/leu.2012.314
State	Published - May 2013
Externally published	Yes

Keywords

Hausp
PTEN
acute myeloid leukemia
suppressor gene

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1038/leu.2012.314

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@article{d3794dc1f34740e4be70d564d89ffd45,

title = "Nucleophosmin/B26 regulates PTEN through interaction with HAUSP in acute myeloid leukemia",

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.",

keywords = "Hausp, PTEN, acute myeloid leukemia, suppressor gene",

author = "Noguera, {N. I.} and Song, {M. S.} and M. Divona and G. Catalano and Calvo, {K. L.} and F. Garc{\'i}a and T. Ottone and F. Florenzano and I. Faraoni and L. Battistini and E. Colombo and S. Amadori and Pandolfi, {P. P.} and F. Lo-Coco",

note = "Funding Information: We are grateful to AM Gruszka (I.F.O.M. Milan) for kindly donating the T26 monoclonal antibody. This work was supported by AIRC (Associazione Italiana per la Ricerca sul Cancro), AIL (Associazione Italiana contro le Leucemie) and ANPCyT– FONCyT (Agencia Nacional de Promoci{\'o}n Cient{\'i}fica y Tecnol{\'o}gica–Fondo para la Investigaci{\'o}n Cient{\'i}fica y Tecnol{\'o}gica, Argentina, PICT 2006-01865). This work was also supported by National Institutes of Health grants to PPP; KLC is a research fellow of the Consejo Nacional de Investigaciones Cient{\'i}ficas y T{\'e}cnicas (CONICET); NIN and FG are established investigators at CONICET.",

year = "2013",

month = may,

doi = "10.1038/leu.2012.314",

language = "English (US)",

volume = "27",

pages = "1037--1043",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Nature Publishing Group",

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T1 - Nucleophosmin/B26 regulates PTEN through interaction with HAUSP in acute myeloid leukemia

AU - Noguera, N. I.

AU - Song, M. S.

AU - Divona, M.

AU - Catalano, G.

AU - Calvo, K. L.

AU - García, F.

AU - Ottone, T.

AU - Florenzano, F.

AU - Faraoni, I.

AU - Battistini, L.

AU - Colombo, E.

AU - Amadori, S.

AU - Pandolfi, P. P.

AU - Lo-Coco, F.

N1 - Funding Information: We are grateful to AM Gruszka (I.F.O.M. Milan) for kindly donating the T26 monoclonal antibody. This work was supported by AIRC (Associazione Italiana per la Ricerca sul Cancro), AIL (Associazione Italiana contro le Leucemie) and ANPCyT– FONCyT (Agencia Nacional de Promoción Científica y Tecnológica–Fondo para la Investigación Científica y Tecnológica, Argentina, PICT 2006-01865). This work was also supported by National Institutes of Health grants to PPP; KLC is a research fellow of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); NIN and FG are established investigators at CONICET.

PY - 2013/5

Y1 - 2013/5

N2 - 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.

AB - 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.

KW - Hausp

KW - PTEN

KW - acute myeloid leukemia

KW - suppressor gene

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U2 - 10.1038/leu.2012.314

DO - 10.1038/leu.2012.314

M3 - Article

C2 - 23183427

AN - SCOPUS:84877594600

SN - 0887-6924

VL - 27

SP - 1037

EP - 1043

JO - Leukemia

JF - Leukemia

IS - 5

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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