1. ¹Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
2. ²Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China
3. ³Department of Emergency Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, NY, USA
4. ⁴Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China

Correspondence: Professor L Cao, Department of Pediatrics, Xiangya Hospital, Central South University, 110 Xiangya Road Changsha, Hunan 410008, People's Republic of China. E-mail: caolizhi318@hotmail.com

Received 23 March 2009; Revised 23 August 2009; Accepted 11 September 2009; Published online 5 November 2009.

Abstract

Bcl-2 proteins are over-expressed in many tumors and are critically important for cell survival. Their anti-apoptotic activities are determined by intracellular localization and post-translational modifications (such as phosphorylation). Here, we showed that WAVE1, a member of the Wiskott–Aldrich syndrome protein family, was over-expressed in blood cancer cell lines, and functioned as a negative regulator of apoptosis. Further enhanced expression of WAVE1 by gene transfection rendered leukemia cells more resistant to anti-cancer drug-induced apoptosis; whereas suppression of WAVE1 expression by RNA interference restored leukemia cells' sensitivity to anti-drug-induced apoptosis. WAVE1 was found to be associated with mitochondrial Bcl-2, and its depletion led to mitochondrial release of Bcl-2, and phosphorylation of ASK1/JNK and Bcl-2. Furthermore, depletion of WAVE1 expression increased anti-cancer drug-induced production of reactive oxygen species in leukemia cells. Taken together, these results suggest WAVE1 as a novel regulator of apoptosis, and potential drug target for therapeutic intervention of leukemia.