WAVE1 regulates Bcl-2 localization and phosphorylation in leukemia cells

R. Kang, D. Tang, Y. Yu, Z. Wang, T. Hu, H. Wang, L. Cao

Research output: Contribution to journalArticle

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)177-186
Number of pages10
JournalLeukemia
Volume24
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Keywords

  • Apoptosis
  • Bcl-2
  • Calcium
  • ROS
  • WAVE1

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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