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Research Article

Plk1-mediated phosphorylation of TSC1 enhances the efficacy of rapamycin

Zhiguo Li, Yifan Kong, Longzhen Song, Qian Luo, Jinghui Liu, Chen Shao, Xianzeng Hou and Xiaoqi Liu
Zhiguo Li
Emory University
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Yifan Kong
Department of Biochemistry, Purdue University
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Longzhen Song
Purdue University
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Qian Luo
Department of Biochemistry, Purdue University
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Jinghui Liu
Purdue University
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Chen Shao
Biochemistry, Purdue University
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Xianzeng Hou
Purdue University
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Xiaoqi Liu
Department of Biochemistry, Purdue University
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  • For correspondence: liu8@purdue.edu
DOI: 10.1158/0008-5472.CAN-17-3046
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Abstract

The AKT/TSC/mTOR axis is an important pathway controlling cell growth, survival and proliferation in response to extracellular cues. Recently, it was reported that AKT activity fluctuates across the cell cycle. However, it remains unclear whether downstream targets of AKT are also regulated by the cell cycle. Here we report that mTORC1 activity inversely correlates with AKT activity during the cell cycle. Mechanistically, Plk1 phosphorylation of TSC1 at S467 and S578 interfered with TSC1/TSC2 binding, destabilized TSC1, promoted dissociation of the TSC complex from the lysosome, and eventually led to mTORC1 activation. Tumors derived from cancer cells expressing the TSC1-S467E/S578E mutant exhibited greater sensitivity to rapamycin than those expressing WT TSC1. Collectively, our data support a model in which Plk1, instead of AKT, regulates the TSC/mTORC1 pathway during mitosis, eventually regulating the efficacy of rapamycin.

  • Received October 3, 2017.
  • Revision received February 13, 2018.
  • Accepted March 15, 2018.
  • Copyright ©2018, American Association for Cancer Research.

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Published OnlineFirst March 20, 2018
doi: 10.1158/0008-5472.CAN-17-3046

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Plk1-mediated phosphorylation of TSC1 enhances the efficacy of rapamycin
Zhiguo Li, Yifan Kong, Longzhen Song, Qian Luo, Jinghui Liu, Chen Shao, Xianzeng Hou and Xiaoqi Liu
Cancer Res March 20 2018 DOI: 10.1158/0008-5472.CAN-17-3046

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Plk1-mediated phosphorylation of TSC1 enhances the efficacy of rapamycin
Zhiguo Li, Yifan Kong, Longzhen Song, Qian Luo, Jinghui Liu, Chen Shao, Xianzeng Hou and Xiaoqi Liu
Cancer Res March 20 2018 DOI: 10.1158/0008-5472.CAN-17-3046
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Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

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