HAUSP compartmentalization in chronic myeloid leukemia

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.