Hepatocyte odd protein shuttling (HOPS) is a bridging protein in the nucleophosmin-p19Arf network

M. Castelli, S. Pieroni, C. Brunacci, D. Piobbico, D. Bartoli, M. M. Bellet, E. Colombo, P. G. Pelicci, M. A. Della Fazia, G. Servillo

Research output: Contribution to journalArticlepeer-review

Abstract

Nucleophosmin (NPM), a ubiquitously and abundantly expressed protein, occurs in the nucleolus, shuttling between the nucleoplasm and cytoplasm. The NPM gene is mutated in almost 30% of human acute myeloid leukemia cells. NPM interacts with p53 and p19Arf, directs localization of p19 Arf in the nucleolus and protects the latter from degradation. Hepatocyte odd protein shuttling (HOPS) is also a ubiquitously expressed protein that moves between the nucleus and cytoplasm. Within the nucleus of resting cells, HOPS overexpression causes cell cycle arrest in G0/G1. HOPS knockdown causes centrosome hyperamplification leading to multinucleated cells and the formation of micronuclei. We demonstrate a direct interaction of HOPS with NPM and p19Arf, resulting in a functionally active trimeric complex. NPM appeared to regulate HOPS half-life, which, in turn, stabilized p19 Arf and controlled its localization in the nucleolus. These findings suggest that HOPS acts as a functional bridge in the interaction between NPM and p19Arf, providing new mechanistic insight into how NPM and p19 Arf will oppose tumor cell proliferation.

Original languageEnglish
Pages (from-to)3350-3358
Number of pages9
JournalOncogene
Volume32
Issue number28
DOIs
Publication statusPublished - Jul 11 2013

Keywords

  • Hepatocyte odd protein shuttling (HOPS)
  • Nucleophosmin (NPM)
  • p19
  • Tmub1
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Fingerprint Dive into the research topics of 'Hepatocyte odd protein shuttling (HOPS) is a bridging protein in the nucleophosmin-p19Arf network'. Together they form a unique fingerprint.

Cite this