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Apoptosis

WAVE1 regulates Bcl-2 localization and phosphorylation in leukemia cells

Leukemia volume 24, pages 177–186 (2010)Cite this article

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.

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Acknowledgements

This work was supported by grants from The National Natural Sciences Foundation of China (30571982, 30772353, 30973234 to LC, 30500485 to DT), Doctoral Program of Higher Education of China (20070533042 to LC), and supported in part by the National Institutes of Health grants (NIH/NIGMS, R01GM063075 and R01GM070817, to HW).

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Authors and Affiliations

  1. Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China

    R Kang, Y Yu, Z Wang, T Hu & L Cao

  2. Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China

    D Tang

  3. Department of Emergency Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, NY, USA

    H Wang

  4. Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China

    H Wang

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  1. R Kang
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Correspondence to L Cao.

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Kang, R., Tang, D., Yu, Y. et al. WAVE1 regulates Bcl-2 localization and phosphorylation in leukemia cells. Leukemia 24, 177–186 (2010). https://doi.org/10.1038/leu.2009.224

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