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Cbl-b promotes chemotherapy-induced apoptosis in rat basophilic leukemia cells by suppressing PI3K/Akt activation and enhancing MEK/ERK activation

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Abstract

The ubiquitin ligase Cbl-b is a negative regulator of the PI3K/Akt pathway, the survival pathway implicated in chemotherapy resistance. However, it remains unclear whether Cbl-b can regulate chemosensitivity through modulating Akt activation. In this study, VP-16-induced RBL-2H3 cells apoptosis was accompanied by the activation of Akt and ERK. The PI3K inhibitor LY294002, not the ERK inhibitor PD98059, enhanced the apoptosis. In addition, down-regulation of Cbl-b was also detected. Over expression of Cbl-b significantly enhanced VP-16-induced cell apoptosis with inhibition of Akt activity, while a dominant negative (DN) RING Finger domain mutation completely abolished this enhancement. On the other hand, ERK activity was enhanced by Cbl-b, and the ERK inhibitor PD98059 reversed Cbl-b-enhanced apoptosis. The consistent results were also showed in the process of Ara-c treatment. These observations indicate that Cbl-b promotes RBL-2H3 apoptosis induced by VP-16 or Ara-c, probably through inhibition of Akt and activation of ERK.

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Acknowledgments

We thank Dr. Hirohei Yamamura and Dr. Kiyonao Sada for kindly providing the reagents. This article was supported by National Natural Science Foundation of China (No. 30770993, No. 30700807).

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Authors and Affiliations

  1. Department of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, 110001, Shenyang, China

    Xiujuan Qu, Yingchun Li, Jing Liu, Ling Xu, Ye Zhang, Kezuo Hou & Yunpeng Liu

  2. Department of Respiratory Medicine, The First Hospital of China Medical University, 110001, Shenyang, China

    Xuejun Hu

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  1. Xiujuan Qu
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  2. Yingchun Li
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Correspondence to Yunpeng Liu.

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Xiujuan Qu and Yingchun Li contributed equally to this article.

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Qu, X., Li, Y., Liu, J. et al. Cbl-b promotes chemotherapy-induced apoptosis in rat basophilic leukemia cells by suppressing PI3K/Akt activation and enhancing MEK/ERK activation. Mol Cell Biochem 340, 107–114 (2010). https://doi.org/10.1007/s11010-010-0407-8

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  • DOI: https://doi.org/10.1007/s11010-010-0407-8

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