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Article

PBK/TOPK mediates promyelocyte proliferation via Nrf2-regulated cell cycle progression and apoptosis

  • Authors:
    • Yuhong Liu
    • Hui Liu
    • Huiqin Cao
    • Bin Song
    • Wen Zhang
    • Wanggang Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
  • Pages: 3288-3296
    |
    Published online on: September 24, 2015
       https://doi.org/10.3892/or.2015.4308
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Abstract

Acute myeloid leukemia (AML) is a disorder involving hematopoietic stem cells, characterized by blockage of hematopoietic cell differentiation and an increase in clonal neoplastic proliferation. AML is associated with poor patient outcome. PBK/TOPK is a protein kinase derived from PDZ-binding kinase (PBK)/T-lymphokine-activated killer (T-LAK) cell-originated protein kinase (TOPK). Previous studies have shown that PBK/TOPK is expressed in hematologic tumors. In the present study, we aimed to investigate the role of PBK/TOPK in promyelocyte proliferation and to clarify the molecular mechanism. PBK/TOPK knockdown (KD) significantly decreased cell proliferation and viability in the NB4 and HL-60 promyelocytes. PBK/TOPK KD resulted in G2/M cell cycle arrest that attributed to a decrease in cdc2 and cyclin B expression. In addition, PBK/TOPK KD caused apoptosis, as evidenced by activation of the mitochondrial apoptotic pathway and an increase in TUNEL-positive cells. PBK/TOPK KD induced mitochondrial dysfunction and ROS generation, and inhibition of mitochondrial dysfunction and ROS production suppressed PBK/TOPK KD-induced cell cycle arrest and apoptosis. Moreover, PBK/TOPK KD decreased Nrf2 expression and ARE-binding activity. Overexpression of Nrf2 inhibited the PBK/TOPK KD-induced decrease in cdc2 and cyclin B expression and cell cycle arrest, and blocked ROS production and apoptosis. Based on literature and our results, it was demonstrated that Nrf2 may be a crucial regulator that mediates PBK/TOPK-exerted promotion of cell proliferation. PBK/TOPK stabilizes Nrf2, strictly regulates the ROS level, promotes cell cycle progression and inhibits apoptosis, contributing to the proliferation of promyelocytes. Our results provide new insights into the molecular mechanism of PBK/TOPK-mediated promyelocyte proliferation and shed light on the pathogenesis of AML.
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Copy and paste a formatted citation
Spandidos Publications style
Liu Y, Liu H, Cao H, Song B, Zhang W and Zhang W: PBK/TOPK mediates promyelocyte proliferation via Nrf2-regulated cell cycle progression and apoptosis. Oncol Rep 34: 3288-3296, 2015.
APA
Liu, Y., Liu, H., Cao, H., Song, B., Zhang, W., & Zhang, W. (2015). PBK/TOPK mediates promyelocyte proliferation via Nrf2-regulated cell cycle progression and apoptosis. Oncology Reports, 34, 3288-3296. https://doi.org/10.3892/or.2015.4308
MLA
Liu, Y., Liu, H., Cao, H., Song, B., Zhang, W., Zhang, W."PBK/TOPK mediates promyelocyte proliferation via Nrf2-regulated cell cycle progression and apoptosis". Oncology Reports 34.6 (2015): 3288-3296.
Chicago
Liu, Y., Liu, H., Cao, H., Song, B., Zhang, W., Zhang, W."PBK/TOPK mediates promyelocyte proliferation via Nrf2-regulated cell cycle progression and apoptosis". Oncology Reports 34, no. 6 (2015): 3288-3296. https://doi.org/10.3892/or.2015.4308
Copy and paste a formatted citation
x
Spandidos Publications style
Liu Y, Liu H, Cao H, Song B, Zhang W and Zhang W: PBK/TOPK mediates promyelocyte proliferation via Nrf2-regulated cell cycle progression and apoptosis. Oncol Rep 34: 3288-3296, 2015.
APA
Liu, Y., Liu, H., Cao, H., Song, B., Zhang, W., & Zhang, W. (2015). PBK/TOPK mediates promyelocyte proliferation via Nrf2-regulated cell cycle progression and apoptosis. Oncology Reports, 34, 3288-3296. https://doi.org/10.3892/or.2015.4308
MLA
Liu, Y., Liu, H., Cao, H., Song, B., Zhang, W., Zhang, W."PBK/TOPK mediates promyelocyte proliferation via Nrf2-regulated cell cycle progression and apoptosis". Oncology Reports 34.6 (2015): 3288-3296.
Chicago
Liu, Y., Liu, H., Cao, H., Song, B., Zhang, W., Zhang, W."PBK/TOPK mediates promyelocyte proliferation via Nrf2-regulated cell cycle progression and apoptosis". Oncology Reports 34, no. 6 (2015): 3288-3296. https://doi.org/10.3892/or.2015.4308
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