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A new role of NUAK1: directly phosphorylating p53 and regulating cell proliferation

Oncogene volume 30, pages 2933–2942 (2011)Cite this article

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Abstract

It has been suggested that adenosine monophosphate-activated protein kinase (AMPK) and 12 AMPK-related kinases (ARK), including novel (nua) kinase family 1 (NUAK1), are activated by master kinase LKB1, a major tumor suppressor. Apart from evidence to suggest that NUAK1 participates in induction of tumor survival, invasion and p53-independent cellular senescence, its detailed biological functions remain unclear. Here we showed that in the presence of wild-type LKB1, NUAK1 directly interacts with and phosphorylates p53 in vitro and in vivo. The phosphorylation of p53 induced by LKB1 required the kinase activity of NUAK1 and phosphorylation of NUAK1 at Thr211 by LKB1 was essential for its kinase activity, which leads to the conclusion that LKB1 activates NUAK1 and regulates phosphorylation of p53 through the NUAK1 kinase, at least partially. LKB1/NUAK1 activation leads to cell cycle arrest at the G1/S border by inducing expression of p21/WAF1. Under the regulation of LKB1, NUAK1 interacts with p53 in the nucleus and binds to the p53-responsive element of p21/WAF1 promoter. These findings have highlighted a novel role for NUAK1 in LKB1-related signaling pathways; NUAK1 can regulate cell proliferation and exert tumor suppression through direct interaction with p53.

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Acknowledgements

We thank Professor Tingmao Hu for helpful discussion. We are grateful to Dr Jinghua Yan for providing the plasmids. This study was supported by the Key Project of the Science and Technology Foundation of Education Ministry of China (209025) and the Key Project of the Inner Mongolia National Natural Science Foundation (2009ZD007).

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Authors and Affiliations

  1. College of Life Sciences, Inner Mongolia University, Huhhot, Inner Mongolia, China

    X Hou, J-E Liu, W Liu, C-Y Liu, Z-Y Liu & Z-Y Sun

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  1. X Hou
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Correspondence to X Hou.

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Hou, X., Liu, JE., Liu, W. et al. A new role of NUAK1: directly phosphorylating p53 and regulating cell proliferation. Oncogene 30, 2933–2942 (2011). https://doi.org/10.1038/onc.2011.19

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