Nucleophosmin/B26 regulates PTEN through interaction with HAUSP in acute myeloid leukemia - PubMed (original) (raw)

. 2013 Apr;27(5):1037-43.

doi: 10.1038/leu.2012.314. Epub 2012 Nov 7.

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

Affiliations

• PMID: 23183427
• DOI: 10.1038/leu.2012.314

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

N I Noguera et al. Leukemia. 2013 Apr.

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.

PubMed Disclaimer

Similar articles

• The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network.
  Song MS, Salmena L, Carracedo A, Egia A, Lo-Coco F, Teruya-Feldstein J, Pandolfi PP. Song MS, et al. Nature. 2008 Oct 9;455(7214):813-7. doi: 10.1038/nature07290. Epub 2008 Aug 20. Nature. 2008. PMID: 18716620 Free PMC article.
• HAUSP compartmentalization in chronic myeloid leukemia.
  Morotti A, Panuzzo C, Crivellaro S, Carrà G, Guerrasio A, Saglio G. Morotti A, et al. Eur J Haematol. 2015 Apr;94(4):318-21. doi: 10.1111/ejh.12422. Epub 2014 Sep 3. Eur J Haematol. 2015. PMID: 25082234
• Altered nucleophosmin transport in acute myeloid leukaemia with mutated NPM1: molecular basis and clinical implications.
  Falini B, Bolli N, Liso A, Martelli MP, Mannucci R, Pileri S, Nicoletti I. Falini B, et al. Leukemia. 2009 Oct;23(10):1731-43. doi: 10.1038/leu.2009.124. Epub 2009 Jun 11. Leukemia. 2009. PMID: 19516275 Review.
• BCR-ABL disrupts PTEN nuclear-cytoplasmic shuttling through phosphorylation-dependent activation of HAUSP.
  Morotti A, Panuzzo C, Crivellaro S, Pergolizzi B, Familiari U, Berger AH, Saglio G, Pandolfi PP. Morotti A, et al. Leukemia. 2014 Jun;28(6):1326-33. doi: 10.1038/leu.2013.370. Epub 2013 Dec 9. Leukemia. 2014. PMID: 24317448
• The equilibrium of tumor suppression: DUBs as active regulators of PTEN.
  Christine A, Park MK, Song SJ, Song MS. Christine A, et al. Exp Mol Med. 2022 Nov;54(11):1814-1821. doi: 10.1038/s12276-022-00887-w. Epub 2022 Nov 16. Exp Mol Med. 2022. PMID: 36385557 Free PMC article. Review.

Cited by

• Ubiquitin-specific proteases (USPs) in leukemia: a systematic review.
  Zangooie A, Tavoosi S, Arabhosseini M, Halimi A, Zangooie H, Baghsheikhi AH, Rahgozar S, Ahmadvand M, Jarrahi AM, Salehi Z. Zangooie A, et al. BMC Cancer. 2024 Jul 25;24(1):894. doi: 10.1186/s12885-024-12614-x. BMC Cancer. 2024. PMID: 39048945 Free PMC article.
• Nucleophosmin mutations in acute myeloid leukemia: a tale of protein unfolding and mislocalization.
  Federici L, Falini B. Federici L, et al. Protein Sci. 2013 May;22(5):545-56. doi: 10.1002/pro.2240. Epub 2013 Mar 18. Protein Sci. 2013. PMID: 23436734 Free PMC article. Review.
• PRL2 inhibition elevates PTEN protein and ameliorates progression of acute myeloid leukemia.
  Carlock C, Bai Y, Paige-Hood A, Li Q, Nguele Meke F, Zhang ZY. Carlock C, et al. JCI Insight. 2023 Oct 9;8(19):e170065. doi: 10.1172/jci.insight.170065. JCI Insight. 2023. PMID: 37665633 Free PMC article.
• Cytoplasmic nucleophosmin has elevated T199 phosphorylation upon which G2/M phase progression is dependent.
  Chan N, Lim TM. Chan N, et al. Sci Rep. 2015 Jun 30;5:11777. doi: 10.1038/srep11777. Sci Rep. 2015. PMID: 26123729 Free PMC article.
• The Role of PTEN in Myeloid Malignancies.
  Morotti A, Panuzzo C, Crivellaro S, Carrà G, Torti D, Guerrasio A, Saglio G. Morotti A, et al. Hematol Rep. 2015 Dec 9;7(4):5844. doi: 10.4081/hr.2015.6027. eCollection 2015 Nov 23. Hematol Rep. 2015. PMID: 26734127 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Nature Publishing Group
  • Ovid Technologies, Inc.

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • SciCrunch