WAVE1 regulates Bcl-2 localization and phosphorylation in leukemia cells.

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.

• Authors: R Kang, D Tang, Y Yu, Z Wang, T Hu, H Wang, L Cao
• Journal: Leukemia (Leukemia) Vol. 24 Issue 1 Pg. 177-86 (Jan 2010) ISSN: 1476-5551 [Electronic] England
• PMID: 19890377 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• BCL2L1 protein, human
• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• WASF1 protein, human
• Wiskott-Aldrich Syndrome Protein Family
• bcl-X Protein
• MAP Kinase Kinase Kinase 5
• MAP3K5 protein, human
• Calcium

Topics

• Apoptosis
• Calcium (metabolism)
• Cell Line, Tumor
• Humans
• Leukemia (drug therapy, metabolism)
• MAP Kinase Kinase Kinase 5 (physiology)
• Phosphorylation
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Reactive Oxygen Species (metabolism)
• Wiskott-Aldrich Syndrome Protein Family (analysis, physiology)
• bcl-X Protein (metabolism)