HAUSP compartmentalization in chronic myeloid leukemia

Eur J Haematol. 2015 Apr;94(4):318-21. doi: 10.1111/ejh.12422. Epub 2014 Sep 3.

Abstract

Introduction: PTEN plays an essential role in the pathogenesis of chronic myeloid leukemia. Recently, we have shown that BCR-ABL promotes PTEN nuclear exclusion, through the modulation of HAUSP activity.

Objectives: Here, we investigate HAUSP cellular compartmentalization in primary CML samples.

Results: While in normal CD34 positive cells HAUSP is expressed mostly in the nucleus, in CML CD34 cells HAUSP is expressed both in the nuclear bodies and in the cytoplasm.

Conclusions: This observation suggests that HAUSP behaves as a shuttling protein in CML. It can bind to BCR-ABL in the cytosol, where it is phosphorylated on tyrosine residues, and it maintains the proper compartmentalization in the nuclear bodies, where it acts as part of a PML network to regulate PTEN de-ubiquitination.

Keywords: HAUSP; PTEN; cellular compartmentalization; chronic myeloid leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / metabolism
  • Gene Expression
  • Humans
  • Intracellular Space / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Protein Binding
  • Protein Transport
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism*
  • Ubiquitin-Specific Peptidase 7

Substances

  • Fusion Proteins, bcr-abl
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • USP7 protein, human
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Peptidase 7