Research Papers:

Induction of apoptosis by directing oncogenic Bcr-Abl into the nucleus

Zheng-Lan Huang, Miao Gao, Qian-Yin Li, Kun Tao, Qing Xiao, Wei-Xi Cao and Wen-Li Feng _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2013; 4:2249-2260. https://doi.org/10.18632/oncotarget.1339

Metrics: PDF 2789 views  |   HTML 2869 views  |   ?  


Zheng-Lan Huang1,*, Miao Gao1,*, Qian-Yin Li1, Kun Tao1, Qing Xiao2, Wei-Xi Cao1, and Wen-Li Feng1

1 Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, Chongqing Medical University, Chongqing, People’s Republic of China.

2 Department of Hematology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China.

* These authors contributed equally to this work.


Wen-Li Feng, email:

Keywords: chronic myeloid leukemia, Bcr-Abl, nuclear localization, rapalog, apoptosis

Received: August 27, 2013 Accepted: October 7, 2013 Published: October 9, 2013


The chimeric Bcr-Abl oncoprotein, which causes chronic myeloid leukemia, mainly localizes in the cytoplasm, and loses its ability to transform cells after moving into the nucleus. Here we report a new strategy to convert Bcr-Abl to be an apoptotic inducer by altering its subcellular localization. We show that a rapalog nuclear transport system (RNTS) containing six nuclear localization signals directs Bcr-Abl into the nucleus and that nuclear entrapped Bcr-Abl induces apoptosis and inhibits proliferation of CML cells by activating p73 and shutting down cytoplasmic oncogenic signals mediated by Bcr-Abl. Coupling cytoplasmic depletion with nuclear entrapment of Bcr-Abl synergistically enhances the inhibitory effect of nuclear Bcr-Abl on its oncogenicity in mice. These results provide evidence that direction of cytoplasmic Bcr-Abl to the nucleus offers an alternative CML therapy.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 1339