1. ¹Virology-Immunology Unit, University of Liège, Liège, Belgium
2. ²Pathology Unit, University of Liège, Liège, Belgium
3. ³Medical Chemistry Unit, CBIG/GIGA, University of Liège, Liège, Belgium
4. ⁴IRIBHM, University of Brussels, Brussels, Belgium

Correspondence: Dr J Piette, CBIG/GIGA, Virology and Immunology Unit, Pathology Institute B23, 4000 Liège, Belgium. E-mail: jpiette@ulg.ac.be

Received 1 December 2005; Revised 3 February 2006; Accepted 28 February 2006; Published online 17 April 2006.

Abstract

Nuclear factor-kappa B (NF-B) is an important prosurvival transcription factor activated in response to a large array of external stimuli, including reactive oxygen species (ROS). Previous works have shown that NF-B activation by ROS involved tyrosine phosphorylation of the inhibitor IB through an IB kinase (IKK)-independent mechanism. In the present work, we investigated with more details NF-B redox regulation in human leukemic cells. By using different cell lines (CEM, Jurkat and the subclone Jurkat JR), we clearly showed that NF-B activation by hydrogen peroxide (H₂O₂) is cell-type dependent: it activates NF-B through tyrosine phosphorylation of IB in Jurkat cells, whereas it induces an IKK-mediated IB phosphorylation on S32 and 36 in CEM and Jurkat JR cells. We showed that this H₂O₂-induced IKK activation in CEM and Jurkat JR cells is mediated by SH2-containing inositol 5'-phosphatase 1 (SHIP-1), a lipid phosphatase that is absent in Jurkat cells. Indeed, the complementation of SHIP-1 in Jurkat cells made them shift to an IKK-dependent mechanism upon oxidative stress stimulation. We also showed that Jurkat cells expressing SHIP-1 are more resistant to H₂O₂-induced apoptosis than the parental cells, suggesting that SHIP-1 has an important role in leukemic cell responses to ROS in terms of signal transduction pathways and apoptosis resistance, which can be of interest in improving ROS-mediated chemotherapies.